Brandes et al. 2023 clinical missense pathogenicity benchmarks (ClinVar and HGMD/gnomAD)
Global ROC-AUC and balanced PRC-AUC of variant effect predictors for pathogenic versus benign missense variants on primary UniProt isoforms.
Results are recorded on the linked protocols, tasks or configurations listed below. Their settings and evaluations are kept separate.
Overview
An explanatory profile has not yet been reviewed for this record.
Consult the linked sources for architecture or protocol details. Missing evidence is not evidence of a missing capability.
Results on linked records
This benchmark has no results of its own in this release. 4 linked records have results. They are not assigned to the underlying benchmark: each record keeps its own settings and evaluations, and its scores are on its own page.
- ClinVar missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2) Protocol · part of this benchmark · 19 evaluations · 38 results
- ClinVar missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2) Protocol · part of this benchmark · 90 evaluations · 180 results
- HGMD/gnomAD missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2) Protocol · part of this benchmark · 19 evaluations · 38 results
- HGMD/gnomAD missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2) Protocol · part of this benchmark · 90 evaluations · 180 results
Methods and evaluation design
Procedure, tasks and evaluated configurations
Baseline coverage
Reference methods help show what a model adds beyond simple controls. We track a null control and a conventional method for each protocol.
0 of 12 active baseline roles have published Rewire measurements in this release. Measurements on a selected protocol do not establish coverage of an entire suite.
Baseline status by linked protocol
- ClinVar missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2) · 0/2 roles measured
- ClinVar missense pathogenicity, ESM1b versus EVE on variants scored by both (Brandes et al. 2023 Fig. 2b, Results text) · 0/2 roles measured
- ClinVar missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2) · 0/2 roles measured
- HGMD/gnomAD missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2) · 0/2 roles measured
- HGMD/gnomAD missense pathogenicity, ESM1b versus EVE on variants scored by both (Brandes et al. 2023 Fig. 2b, Results text) · 0/2 roles measured
- HGMD/gnomAD missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2) · 0/2 roles measured
Protocol coverage CSV (gzip) · Model evaluation matrix (gzip) · Source table (gzip) · Release and checksums (gzip)
Coverage is derived from release 2026-10-22-1b7cf027e4f6. Source citations describe the original records; they do not validate an unreviewed baseline proposal. No results have been generated by this audit.
Run instructions
No runnable recipe has been reviewed for this benchmark. Dataset access, model requirements, licences and compute requirements must be checked against its sources before execution.
Strengths, limitations and unresolved questions
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.
0 evidence rows matching the loaded filters
| Property and statement | Original source and location | Review and provenance |
|---|
No evidence rows match these filters. Choose another scope or clear the search.
Sources and history
Release 2026-10-22-1b7cf027e4f6 · Record review: source checked
3 source records and release history
- Genome-wide prediction of disease variant effects with a deep protein language model (Brandes et al., Nature Genetics 2023) · Original source · Version of record, Nature Genetics 55, 1512-1522 (published 2023-08-10)
- Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods · Original source · Version of record, Nature Genetics 55, 1512-1522 (published 2023-08-10)
- Brandes et al. 2023 Supplementary Information (Supplementary Table 1 and Methods) · Original source · Version of record, Nature Genetics 55, 1512-1522 (published 2023-08-10)
Technical metadata and extraction receipts
Stable ID: gfm-guides-20261014-esm1b-benchmark-brandes2023-clinical-missense
- areas
- dna-genomes; protein-function
- contexts
- clinical_research
- entity level
- suite
- version
- Nature Genetics 2023 version of record
- task
- Missense variant pathogenicity classification
- scope note
- Two labelled sets (ClinVar; HGMD disease-causing versus gnomAD common). Extracted: the common-variant comparison of the 19 methods eligible for clinical benchmarking (Supplementary Table 2 columns AUC_AUROC and AUC_Balanced_AUPRC) and the ESM1b versus EVE ROC-AUCs quoted in the Results.
- source locator
- Results paragraphs 1, 2 and 5 of 'ESM1b outperforms other VEP methods...'; Supplementary Table 2 'Contents'
Related records
- part of: ClinVar missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2)
- part of: ClinVar missense pathogenicity, ESM1b versus EVE on variants scored by both (Brandes et al. 2023 Fig. 2b, Results text)
- part of: ClinVar missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2)
- part of: HGMD/gnomAD missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2)
- part of: HGMD/gnomAD missense pathogenicity, ESM1b versus EVE on variants scored by both (Brandes et al. 2023 Fig. 2b, Results text)
- part of: HGMD/gnomAD missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2)