Evidence claim

Relevance of vep-lit-20261014-protocol-proteingym-clinical-zero-shot-substitutions-auc-144fe22 to use-case-missense-pp3-bp4-calibrated-evidence

Use case: Use calibrated computational evidence for missense variants (PP3/BP4)
Assessed by: ProteinGym clinical substitutions, zero-shot, average AUC (commit 144fe22)
Relevance: Proxy evidence
Endpoint: Average over proteins of AUC separating pathogenic from benign clinical substitutions, zero-shot models

Relevance judgement drafted by the extraction agent; independently reviewed, automated review only.

13 reviewed evaluations

Evidence

Source checking verifies the cited claim or transcription. It does not establish independent reproduction.

Evidence table

Inspect claims, sources and review details

Trace each statement to its source and review. A context-only reference supports the record generally; it does not verify an individual field. Source checking does not reproduce an experiment.

One row per statement and cited source. Multiple citations are not independent evaluations. Shared locators are labelled explicitly.

38 evidence rows matching the loaded filters

Claims, original sources and review scope · Release 2026-10-22-1b7cf027e4f6
Property and statement	Original source and location	Review and provenance
Citation locations 2 values source id vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22 locator Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106 source id profile-protocol-proteingym-paper-xml-a58110e0 locator ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity') Context-only references	Protocol metadata evidence: proteingym-paper.xml Original source ↗ vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22: Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106; profile-protocol-proteingym-paper-xml-a58110e0: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity') Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC10723403 retrieved 2026-09-23 Retrieved: 2026-09-23T18:43:10.260678+00:00	not individually reviewed No individual claim review recorded Audit details Field: `attributes.citation_locators` Source artifact SHA-256: `a58110e02c3efc8395c534d48630f577c3d45e90d48198b7f9989cf52600b045` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
Citation locations 2 values source id vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22 locator Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106 source id profile-protocol-proteingym-paper-xml-a58110e0 locator ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity') Context-only references	ProteinGym clinical zero-shot substitutions AUC summary at commit 144fe22 Original source ↗ vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22: Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106; profile-protocol-proteingym-paper-xml-a58110e0: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity') Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: 144fe22b07dfaeec2b366f2346203a9838a55b4c Retrieved: 2026-10-14T13:39:33Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.citation_locators` Source artifact SHA-256: `fbe453d1aaa6c30a1d0adf610f7fc23c36044a8e2548b178d316777383f8fe93` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
Comparison group proteingym-clinical-144fe22 Context-only references	Protocol metadata evidence: proteingym-paper.xml Original source ↗ vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22: Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106; profile-protocol-proteingym-paper-xml-a58110e0: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity') Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC10723403 retrieved 2026-09-23 Retrieved: 2026-09-23T18:43:10.260678+00:00	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_group` Source artifact SHA-256: `a58110e02c3efc8395c534d48630f577c3d45e90d48198b7f9989cf52600b045` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
Comparison group proteingym-clinical-144fe22 Context-only references	ProteinGym clinical zero-shot substitutions AUC summary at commit 144fe22 Original source ↗ vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22: Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106; profile-protocol-proteingym-paper-xml-a58110e0: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity') Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: 144fe22b07dfaeec2b366f2346203a9838a55b4c Retrieved: 2026-10-14T13:39:33Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_group` Source artifact SHA-256: `fbe453d1aaa6c30a1d0adf610f7fc23c36044a8e2548b178d316777383f8fe93` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
Comparison title ProteinGym clinical benchmark (commit 144fe22) Context-only references	Protocol metadata evidence: proteingym-paper.xml Original source ↗ vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22: Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106; profile-protocol-proteingym-paper-xml-a58110e0: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity') Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC10723403 retrieved 2026-09-23 Retrieved: 2026-09-23T18:43:10.260678+00:00	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_title` Source artifact SHA-256: `a58110e02c3efc8395c534d48630f577c3d45e90d48198b7f9989cf52600b045` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
Comparison title ProteinGym clinical benchmark (commit 144fe22) Context-only references	ProteinGym clinical zero-shot substitutions AUC summary at commit 144fe22 Original source ↗ vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22: Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106; profile-protocol-proteingym-paper-xml-a58110e0: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity') Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: 144fe22b07dfaeec2b366f2346203a9838a55b4c Retrieved: 2026-10-14T13:39:33Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.comparison_title` Source artifact SHA-256: `fbe453d1aaa6c30a1d0adf610f7fc23c36044a8e2548b178d316777383f8fe93` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
Constraints 3 values Inspect every linked evaluation's source locator before citing a result. Do not combine this mapping's evaluations with any other protocol's results. Compare rows only within this protocol. Context-only references	Protocol metadata evidence: proteingym-paper.xml Original source ↗ vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22: Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106; profile-protocol-proteingym-paper-xml-a58110e0: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity') Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC10723403 retrieved 2026-09-23 Retrieved: 2026-09-23T18:43:10.260678+00:00	not individually reviewed No individual claim review recorded Audit details Field: `attributes.constraints` Source artifact SHA-256: `a58110e02c3efc8395c534d48630f577c3d45e90d48198b7f9989cf52600b045` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
Constraints 3 values Inspect every linked evaluation's source locator before citing a result. Do not combine this mapping's evaluations with any other protocol's results. Compare rows only within this protocol. Context-only references	ProteinGym clinical zero-shot substitutions AUC summary at commit 144fe22 Original source ↗ vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22: Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106; profile-protocol-proteingym-paper-xml-a58110e0: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity') Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: 144fe22b07dfaeec2b366f2346203a9838a55b4c Retrieved: 2026-10-14T13:39:33Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.constraints` Source artifact SHA-256: `fbe453d1aaa6c30a1d0adf610f7fc23c36044a8e2548b178d316777383f8fe93` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
Endpoint Average over proteins of AUC separating pathogenic from benign clinical substitutions, zero-shot models Context-only references	Protocol metadata evidence: proteingym-paper.xml Original source ↗ vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22: Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106; profile-protocol-proteingym-paper-xml-a58110e0: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity') Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: PMC10723403 retrieved 2026-09-23 Retrieved: 2026-09-23T18:43:10.260678+00:00	not individually reviewed No individual claim review recorded Audit details Field: `attributes.endpoint` Source artifact SHA-256: `a58110e02c3efc8395c534d48630f577c3d45e90d48198b7f9989cf52600b045` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
Endpoint Average over proteins of AUC separating pathogenic from benign clinical substitutions, zero-shot models Context-only references	ProteinGym clinical zero-shot substitutions AUC summary at commit 144fe22 Original source ↗ vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22: Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106; profile-protocol-proteingym-paper-xml-a58110e0: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity') Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: 144fe22b07dfaeec2b366f2346203a9838a55b4c Retrieved: 2026-10-14T13:39:33Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.endpoint` Source artifact SHA-256: `fbe453d1aaa6c30a1d0adf610f7fc23c36044a8e2548b178d316777383f8fe93` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact

How to read the evidence

Sources and history

Release 2026-10-22-1b7cf027e4f6 · Record review: source checked

2 source records and release history

Protocol metadata evidence: proteingym-paper.xml · Original source · PMC10723403 retrieved 2026-09-23
ProteinGym clinical zero-shot substitutions AUC summary at commit 144fe22 · Original source · 144fe22b07dfaeec2b366f2346203a9838a55b4c

Download this release (gzip)

Technical metadata and extraction receipts

Stable ID: use-case-mapping-vep-uc-20261014-missense-pp3-bp4-calibrated-evidence-proteingym-clinical-zero-shot-substitutions-auc-144fe22

field: links:assessed_by:vep-lit-20261014-protocol-proteingym-clinical-zero-shot-substitutions-auc-144fe22
value: vep-lit-20261014-protocol-proteingym-clinical-zero-shot-substitutions-auc-144fe22
relevance: proxy
endpoint: Average over proteins of AUC separating pathogenic from benign clinical substitutions, zero-shot models
rationale: Proxy: discrimination of ClinVar missense labels by zero-shot models, some of which are calibration candidates (for example ESM1b); no thresholds or evidence strengths.
constraints: Inspect every linked evaluation's source locator before citing a result.; Do not combine this mapping's evaluations with any other protocol's results.; Compare rows only within this protocol.
limitations: Only 13 models are listed; the file's completeness is not stated.; Averaging and uncertainty construction not verified for the clinical summaries.; Clinical labels are biased towards heavily studied proteins, such as well-known cancer genes, and towards European ancestry (ProteinGym paper, Limitations).; Evolutionary conservation is one of the criteria used to classify ClinVar variants, so even zero-shot models are not free of circularity (ProteinGym paper, Limitations).; Per-protein AUC averaged over proteins does not test whether scores are comparable across genes, which genome-wide thresholds assume.; The ProteinGym paper describes the 2023 clinical sets; whether the sets behind the 144fe22 files are unchanged is not stated.; Transcribed from the source; no reproduction by Rewire and no human scientific review.
citation locators: source id: vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22; locator: Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106; source id: profile-protocol-proteingym-paper-xml-a58110e0; locator: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity')
source locator: vep-lit-20261014-source-proteingym-clinical-zero-shot-substitutions-auc-summary-144fe22: Summary_performance_clinical_substitutions_AUC.csv (zero-shot); README lines 22-28, 106; profile-protocol-proteingym-paper-xml-a58110e0: ProteinGym NeurIPS 2023 paper (PMC10723403): 'Clinical datasets', Appendix A.3.2, Appendix 'Limitations' ('Bias', 'Circularity')
headline metric: auroc
comparison group: proteingym-clinical-144fe22
comparison title: ProteinGym clinical benchmark (commit 144fe22)
stratum label: Substitutions, zero-shot
stratum order: 1
reason: VEP use-case pass 2026-10-14: relevance of a protocol to a new use case (rewire-benchmark-data #151/#152).
review: reviewer: claude; reviewer note: Claude review agent; no human review claimed. Independent Claude (Opus 5.5) review agent, separate from the extraction agent that built this batch. Automated review only. Transcription, not reproduction.; reviewed at: 2026-10-14T16:00:00Z; method: ai-assisted-source-review; scope-review; method note: Checked the endpoint against the use case's question, inputs, exclusions and output; checked each limitation and number against the cited sources, re-downloaded and hash-matched; listed every evaluation on the protocol in reviewed_evaluations (values of evaluations already in the store were checked by their own independent reviews).; note: Judgement drafted by the extraction agent and revised in review (docs/reviews/vep-use-cases-2026-10-14-review.md).
reviewed evaluations: vep-lit-20261014-eval-pg-czs-esm-1b; vep-lit-20261014-eval-pg-czs-gemme; vep-lit-20261014-eval-pg-czs-poet-200m; vep-lit-20261014-eval-pg-czs-proteingym-clinical-eve; vep-lit-20261014-eval-pg-czs-proteingym-clinical-list-s2; vep-lit-20261014-eval-pg-czs-proteingym-clinical-lrt; vep-lit-20261014-eval-pg-czs-proteingym-clinical-mutationassessor; vep-lit-20261014-eval-pg-czs-proteingym-clinical-mutpred; vep-lit-20261014-eval-pg-czs-proteingym-clinical-primateai; vep-lit-20261014-eval-pg-czs-proteingym-clinical-provean; vep-lit-20261014-eval-pg-czs-proteingym-clinical-sift; vep-lit-20261014-eval-pg-czs-proteingym-clinical-sift4g; vep-lit-20261014-eval-pg-czs-trancepteve-l
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subject: Use calibrated computational evidence for missense variants (PP3/BP4)

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