Share of gnomAD variants called pathogenic at developer thresholds (Pejaver et al. 2022 Table 3)
Fraction of the gnomAD reference set that SIFT, PolyPhen-2 and CADD call pathogenic at their default thresholds, against a prior probability of pathogenicity of 4.41%.
Overview
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3 recorded evaluations, 3 metric rows. A comparison chart has not yet been validated for these results. The table retains the individual findings and their sources.
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All evaluations
3 evaluations · 3 results. Different protocols are not a single leaderboard.
Protocol: Share of gnomAD variants called pathogenic at developer thresholds (Pejaver et al. 2022 Table 3) · Dataset: gnomAD reference set (Pejaver et al. 2022)
In source order. Decimals are rounded for display; each value links to the printed value and its source.
| Tested configuration | Proportion (gnomAD-set variants predicted pathogenic at the developer threshold) |
|---|---|
| CADD (Pejaver et al. 2022 calibration)Evaluation | 0.651 |
| PolyPhen-2 (Pejaver et al. 2022 calibration)Evaluation | 0.293 |
| SIFT (Pejaver et al. 2022 calibration)Evaluation | 0.504 |
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| Tested configuration | Protocol and dataset | Finding | Evidence and details |
|---|---|---|---|
| Configuration: CADD (Pejaver et al. 2022 calibration) | Protocol: Share of gnomAD variants called pathogenic at developer thresholds (Pejaver et al. 2022 Table 3) Dataset: gnomAD reference set (Pejaver et al. 2022) | 0.651 Proportion (gnomAD-set variants predicted pathogenic at the developer threshold) fraction · unknown Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceCADD at developer threshold 20.000: gnomAD fraction called pathogenic (Pejaver et al. 2022) vep-uc-20261014-protocol-pejaver2022-developer-threshold-gnomad-fraction Aggregation: Not reported Pejaver et al. 2022, Am J Hum Genet 109:2163 (Europe PMC full text XML) · Table 3, row 'CADD', column 'Fraction of predicted pathogenic variants in the gnomAD set' |
| Configuration: PolyPhen-2 (Pejaver et al. 2022 calibration) | Protocol: Share of gnomAD variants called pathogenic at developer thresholds (Pejaver et al. 2022 Table 3) Dataset: gnomAD reference set (Pejaver et al. 2022) | 0.293 Proportion (gnomAD-set variants predicted pathogenic at the developer threshold) fraction · unknown Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourcePolyPhen-2 at developer threshold 0.902: gnomAD fraction called pathogenic (Pejaver et al. 2022) vep-uc-20261014-protocol-pejaver2022-developer-threshold-gnomad-fraction Aggregation: Not reported Pejaver et al. 2022, Am J Hum Genet 109:2163 (Europe PMC full text XML) · Table 3, row 'PolyPhen-2', column 'Fraction of predicted pathogenic variants in the gnomAD set' |
| Configuration: SIFT (Pejaver et al. 2022 calibration) | Protocol: Share of gnomAD variants called pathogenic at developer thresholds (Pejaver et al. 2022 Table 3) Dataset: gnomAD reference set (Pejaver et al. 2022) | 0.504 Proportion (gnomAD-set variants predicted pathogenic at the developer threshold) fraction · unknown Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible | Independent external evaluation · Source checkedMethods, coverage and sourceSIFT at developer threshold 0.050: gnomAD fraction called pathogenic (Pejaver et al. 2022) vep-uc-20261014-protocol-pejaver2022-developer-threshold-gnomad-fraction Aggregation: Not reported Pejaver et al. 2022, Am J Hum Genet 109:2163 (Europe PMC full text XML) · Table 3, row 'SIFT', column 'Fraction of predicted pathogenic variants in the gnomAD set' |
Source checking is not independent reproduction. Release 2026-10-22-1b7cf027e4f6.
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Sources and history
Release 2026-10-22-1b7cf027e4f6 · Record review: source checked
1 source record and release history
- Pejaver et al. 2022, Am J Hum Genet 109:2163 (Europe PMC full text XML) · Original source · PMC9748256 (Am J Hum Genet 2022;109(12):2163)
Technical metadata and extraction receipts
Stable ID: vep-uc-20261014-protocol-pejaver2022-developer-threshold-gnomad-fraction
- areas
- dna-genomes
- contexts
- clinical_research
- protocol
- Count the fraction of gnomAD-set variants at or beyond each tool's developer-recommended pathogenicity threshold.
- task
- Over-calling at developer thresholds
- metric
- proportion
- metric direction
- unknown
- unit
- fraction
- metric qualifier
- gnomAD-set variants predicted pathogenic at the developer threshold
- version
- Pejaver et al. 2022, Table 3
- publication status
- peer_reviewed
- denominator
- 363894
- source locator
- Table 3, last column; Results 'Investigation of commonly used developer-recommended thresholds'
- limitations
- The gnomAD set is unlabelled; a fraction above the 4.41% prior suggests, but does not measure, false positive calls (Results).; Neither direction is better in itself: the authors compare the fraction with the 4.41% prior, and a fraction below the prior would not show a better tool (Results).
- 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; artifact sha256: a78c7bcaacb0ccb72291264bbe7c1f9a16867b0c6207dcbb45c3c59a14af6b3b; retrieval url: https://www.ebi.ac.uk/europepmc/webservices/rest/PMC9748256/fullTextXML; method: source-hash-verification; ai-assisted-source-review; method note: Checked against the Methods, table captions and author lists of the pinned sources.; note: Checked; see the dated review for rulings on origin and carried-over rows.
Related records
- part of: ClinGen SVI calibration of computational predictors for PP3/BP4
- uses data: gnomAD reference set (Pejaver et al. 2022)
- assessed by: Use calibrated computational evidence for missense variants (PP3/BP4)
- assessment: CADD at developer threshold 20.000: gnomAD fraction called pathogenic (Pejaver et al. 2022)
- assessment: PolyPhen-2 at developer threshold 0.902: gnomAD fraction called pathogenic (Pejaver et al. 2022)
- assessment: SIFT at developer threshold 0.050: gnomAD fraction called pathogenic (Pejaver et al. 2022)