← all readouts

Failed Capability Disclosure: ClinVar Pathogenic vs Benign Variant Frequency at GJB2

Exact input: For GJB2, do ClinVar-pathogenic variants sit at lower gnomAD population frequency than benign ones?

Execution template: population allele freq

execution observatory

Attempt 1 of 1

failed Failed · publish stage
committed record

immutable execution contract

exact input
For GJB2, do ClinVar-pathogenic variants sit at lower gnomAD population frequency than benign ones?
execution template
population allele freq
  1. scope
  2. dataset
  3. run
  4. write
  5. review
  6. correct
  7. publish

latest committed step

orchestration Opencode process exited.

wrapper_exited · run · observed · wrapper

committed steps
23
accepted / verified
4
warnings / rejects
1
elapsed
10 minutes
last recorded
tokens recorded
not recorded
data downloaded
not recorded

retained execution history

Every attempt

Latest attempt
  1. Attempt 1 failed Jul 25, 2026 · 09:10 Failed Capability Disclosure: ClinVar Pathogenic vs Benign Variant Frequency at GJB2

canonical execution ledger

Every committed step

Public execution facts only — never private model reasoning, prompts, or raw process output.

attempt-1-ledger hal9000/run/e6a4c487/1 chronological · persisted · archived Reload
  1. 001 orchestration run_queued run · queued · rails Execution attempt 1 queued.
  2. 002 triage investigation_selected notice · observed · rails Capability gate passed with population_allele_freq. Selected by daily triage (score 10): Genomics hypothesis; measurable with public data or a reproducible computational experiment.
    reason code
    supported_template_match
    reference template
    population_allele_freq
  3. 003 exploration neighbor_ideas_accepted artifact · accepted · rails Explored the seed idea and queued 2 undervalued hypotheses for future runs.
    idea count
    2
  4. 004 orchestration run_claimed run · claimed · rails Engine claimed this execution attempt.
  5. 005 orchestration runner_launch_authorized run · started · rails Execution lease acquired; the runner may launch once.
  6. 006 orchestration wrapper_started run · started · wrapper Opencode process started for this exact attempt.
    timeout s
    1200
  7. 007 scoping scope_started action · started · agent Beginning scoping for this exact execution attempt.
  8. 008 scoping scope_proposed gate · proposed · agent No compatible analysis: population_allele_freq tests frequency differences across 1000G super-populations for a single variant, not pathogenic vs benign frequency differences.
    question
    For GJB2, do ClinVar-pathogenic variants sit at lower gnomAD population frequency than benign ones?
  9. 009 writing draft_started action · started · agent Building the initial paper from committed evidence.
    artifact role
    paper_draft
  10. 010 writing draft_written artifact · proposed · agent Wrote the initial paper draft from the available evidence.
    artifact role
    paper_draft
    sha256
    1f62d68f0c7abff0cb8d430dcc7e7306aca40d6efe9038b7c9d562b9ad3d0c3c
  11. 011 review review_started action · started · agent Adversarial review round 1 against every available source artifact.
    artifact role
    paper_review
  12. 012 review review_observed gate · observed · agent Round 1 review severity counts.
    blockers
    0
    majors
    1
    minors
    2
  13. 013 correction correction_started action · started · agent Evidence-preserving corrections for round 1 findings.
    artifact role
    corrected_paper
  14. 014 correction correction_observed gate · observed · agent Round 1 correction resolution counts.
    remaining
    0
    resolved
    3
  15. 015 review review_started action · started · agent Adversarial review round 2 of the corrected paper against every available source artifact.
    artifact role
    paper_review
  16. 016 review review_observed gate · observed · agent Round 2 review: PASS — 0 blockers, 0 majors, 0 minors.
    blockers
    0
    majors
    0
    minors
    0
  17. 017 publishing publication_started action · started · agent Assembling the corrected artifacts for terminal validation.
    artifact role
    terminal_payload
  18. 018 scoping scope_accepted gate · accepted · rails Accepted the run's scoped research question.
    question
    For GJB2, do ClinVar-pathogenic variants sit at lower gnomAD population frequency than benign ones?
  19. 019 data datasets_accepted artifact · accepted · rails Accepted 0 dataset provenance records for this run.
    artifact role
    dataset_provenance
    dataset count
    0
  20. 020 publishing paper_accepted artifact · accepted · rails Accepted the run-owned paper for publication.
    artifact role
    paper
  21. 021 publishing run_published run · failed · rails Execution attempt 1 published with outcome failed.
  22. 022 orchestration wrapper_duration metric · observed · wrapper Measured opencode process duration.
    duration s
    622
  23. 023 orchestration wrapper_exited run · observed · wrapper Opencode process exited.
    exit status
    0

exact-attempt artifacts

Artifacts & paper

Nothing on this attempt is borrowed from a newer run.

Abstract

hal9000/run/e6a4c487/attempt/1 · published Jul 25, 2026

We scoped the question: For GJB2, do ClinVar-pathogenic variants sit at lower gnomAD population frequency than benign ones? This question requires (1) retrieving ClinVar variants classified as pathogenic or benign for gene GJB2, (2) joining them to gnomAD allele-frequency data, and (3) statistically comparing the allele-frequency distributions of the two pathogenicity classes. The capability gate selected the population_allele_freq reference template, which tests whether a single variant or region differs in allele frequency across 1000 Genomes super-populations using a chi-square test and pairwise Fst. This template operates on 1000 Genomes data and asks an entirely different question — super-population differentiation at a locus — than the one we scoped. This sprint reports a failed outcome due to a capability mismatch. No data were fetched, no analysis was run, and no figure was produced.

Failed Capability Disclosure: ClinVar Pathogenic vs Benign Variant Frequency at GJB2

Sprint 23, Run 24

Abstract

We scoped the question: For GJB2, do ClinVar-pathogenic variants sit at lower gnomAD population frequency than benign ones? This question requires (1) retrieving ClinVar variants classified as pathogenic or benign for gene GJB2, (2) joining them to gnomAD allele-frequency data, and (3) statistically comparing the allele-frequency distributions of the two pathogenicity classes. The capability gate selected the population_allele_freq reference template, which tests whether a single variant or region differs in allele frequency across 1000 Genomes super-populations using a chi-square test and pairwise Fst. This template operates on 1000 Genomes data and asks an entirely different question — super-population differentiation at a locus — than the one we scoped. This sprint reports a failed outcome due to a capability mismatch. No data were fetched, no analysis was run, and no figure was produced.

Introduction

GJB2 (gap junction protein beta 2, encoding connexin 26) is the most commonly mutated gene in autosomal recessive non-syndromic hearing loss. ClinVar classifies variants as pathogenic, likely pathogenic, benign, or likely benign, while gnomAD provides population-level allele-frequency data. A natural question is whether pathogenic GJB2 variants are rarer (lower allele frequency) in the general population than benign ones — which would be expected if pathogenic variants are subject to purifying selection.

Methods

Scoped Question

For GJB2, do ClinVar-pathogenic variants sit at lower gnomAD population frequency than benign ones?

Required Analysis

The capability gate assigned population_allele_freq, which performs:

  1. Chi-square test of allele-count homogeneity across five 1000 Genomes super-populations (AFR, AMR, EAS, EUR, SAS) for the lead variant in a region.
  2. Pairwise Hudson Fst between all super-population pairs for the lead variant.
  3. Grouped bar chart of per-super-population allele frequency for the lead variant.

This template uses the fetch_1000g.py fetcher (1000 Genomes phase-3 VCF tabix slices) and consumes a --kg CSV of per-super-population allele frequencies.

Capability Mismatch

The population_allele_freq template cannot answer the scoped question for two structural reasons:

  1. Wrong data source. The template uses 1000 Genomes, not ClinVar or gnomAD. It does not retrieve pathogenicity classifications or gene-specific allele frequencies.
  2. Wrong statistical question. The template tests whether a single variant's allele frequency varies across five continental populations (a between-population test). The scoped question asks whether variants of different pathogenicity classes differ in allele frequency (a between-category test requiring ClinVar labels and gnomAD frequencies).

No amount of data retrieval or script adaptation can make this template answer the original question without fabricating a fundamentally different analysis — which violates the honesty constraint.

Results

No data were fetched. No analysis was performed. No figure was produced. The pipeline stopped at the scoping stage upon identifying an irreconcilable capability mismatch between the assigned template and the question.

Discussion

A template that joins ClinVar pathogenicity labels to gnomAD allele frequencies and compares them would be needed to answer this question. The capability gate would need to assign such a template for this idea to proceed beyond scoping. In this run, the assigned template (population_allele_freq) cannot serve this purpose, so the sprint correctly stopped at the scoping stage.

Limitations

  • This paper contains no empirical findings; it is a capability disclosure only.
  • The mismatch is structural (wrong template for the question), not a transient failure.
  • No analysis artifacts (stats.json, script, figure, or dataset provenance) were produced during this run.

Provenance

  • Sprint ID: 23
  • Run ID: 24
  • Idea: For GJB2, do ClinVar-pathogenic variants sit at lower gnomAD population frequency than benign ones?
  • Assigned template: population_allele_freq
  • Outcome: failed (capability mismatch)
  • Datasets fetched: None
  • Analysis script: None (analysis was not attempted)
  • Seeds: None
  • No analysis artifacts were produced during this run.
Provenance · exact attempt
attempt 1 · exact retained execution
exact input For GJB2, do ClinVar-pathogenic variants sit at lower gnomAD population frequency than benign ones?
execution template population allele freq
script sha256 —
seed —
app git sha 90235e290363ee8922771b653ade6ffe7248ff2f
corrections none

No analysis script — sprint stopped before authoring one.

deterministic re-runs of this exact attempt

Reproduction attempts

Executor health and scientific verdict are separate. Public-safe summaries only; leases and raw process output are never shown.

No reproduction attempt recorded

This exact run has not yet entered the deterministic re-run queue. Its original ledger, artifacts, and provenance remain available above.

Keyboard shortcuts

  • Cmd/Ctrl+K
    Focus global search
  • ?
    Open keyboard shortcuts

Send feedback

We'll only use this to respond to your feedback.