Evaluation

AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75, BRCA1 MAVE evidence strength (Ramadane-Morchadi et al. 2025)

Published in silico evidence comparison for BRCA1/BRCA2 missense variants; transcribed, not reproduced.

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Release 2026-10-10-84341e0b121f · Evidence verified: Not verified

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Evaluation results

1 evaluation · 3 results. Different protocols are not a single leaderboard.

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Tested model or methodProtocolDatasetEvaluation setupMetricEvidence origin

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Exact evaluated configurations and original reported results
Tested configuration	Protocol and dataset	Finding	Evidence and details
Configuration: AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75 (Ramadane-Morchadi et al. 2025)	Protocol: BRCA1 MAVE PP3/BP4 evidence strength by score threshold (Ramadane-Morchadi et al. 2025 Table 1) Dataset: BRCA1 RING and BRCT missense variants with saturation genome editing functional class (Findlay et al. 2018), LoF versus FUNC	−2.914 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -3.354 to -2.474 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75, BRCA1 MAVE evidence strength (Ramadane-Morchadi et al. 2025) brca-20261009-protocol-ramadane2025-pp3-bp4 Aggregation: Not reported ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence · Table 1, row 5 ('AM' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)'
Configuration: AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75 (Ramadane-Morchadi et al. 2025)	Protocol: BRCA1 MAVE PP3/BP4 evidence strength by score threshold (Ramadane-Morchadi et al. 2025 Table 1) Dataset: BRCA1 RING and BRCT missense variants with saturation genome editing functional class (Findlay et al. 2018), LoF versus FUNC	5% proportion percent · lower Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75, BRCA1 MAVE evidence strength (Ramadane-Morchadi et al. 2025) brca-20261009-protocol-ramadane2025-pp3-bp4 Aggregation: Not reported ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence · Table 1, row 5 ('AM' group), column 'No bioinformatic code applicable'
Configuration: AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75 (Ramadane-Morchadi et al. 2025)	Protocol: BRCA1 MAVE PP3/BP4 evidence strength by score threshold (Ramadane-Morchadi et al. 2025 Table 1) Dataset: BRCA1 RING and BRCT missense variants with saturation genome editing functional class (Findlay et al. 2018), LoF versus FUNC	2.81 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.578 to 3.042 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75, BRCA1 MAVE evidence strength (Ramadane-Morchadi et al. 2025) brca-20261009-protocol-ramadane2025-pp3-bp4 Aggregation: Not reported ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence · Table 1, row 5 ('AM' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)'

Source checking is not independent reproduction. Release 2026-10-10-84341e0b121f.

Evaluation procedure

brca-20261009-protocol-ramadane2025-pp3-bp4

Configuration: AlphaMissense, BP4 ≤0.65 and PP3 ≥0.75 (Ramadane-Morchadi et al. 2025)
Protocol: BRCA1 MAVE PP3/BP4 evidence strength by score threshold (Ramadane-Morchadi et al. 2025 Table 1)
Dataset: BRCA1 RING and BRCT missense variants with saturation genome editing functional class (Findlay et al. 2018), LoF versus FUNC

origin: Independent external evaluation
configuration: Primary source as retrieved 2026-10-09
protocol id: brca-20261009-protocol-ramadane2025-pp3-bp4
dataset version: Not reported
split: Whole dataset
population: 1,519 BRCA1 RING and BRCT missense variants: 337 LoF and 1,182 FUNC by MAVE score; 119 intermediate variants excluded
inputs: Missense variant (and structure for ΔΔG)
adaptation: Thresholds chosen on this dataset for AlphaMissense rows 2-3 and ΔΔG; developer thresholds for AlphaMissense row 1; VCEP thresholds for BayesDel
metric implementation: Log2 likelihood ratio of LoF versus FUNC within each score range, with 95% CI
aggregation: Pooled over variants
budget: Not reported

Metadata review: source checked. Unreported conditions prevent automatic comparisons.

Reproduction

Split: Whole dataset
Adaptation: Thresholds chosen on this dataset for AlphaMissense rows 2-3 and ΔΔG; developer thresholds for AlphaMissense row 1; VCEP thresholds for BayesDel
Scoring implementation: Log2 likelihood ratio of LoF versus FUNC within each score range, with 95% CI

No execution recipe has been verified for this exact configuration and evaluation. A benchmark's general instructions may use different inputs, splits or model settings.

Reproducing this published result requires matching its model configuration, data, split and scorer. Source checking or a successful smoke test does not establish score reproduction.

Evidence

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Evidence table

Inspect claims, sources and review details

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18 evidence rows matching the loaded filters

Claims, original sources and review scope · Release 2026-10-10-84341e0b121f
Property and statement	Original source and location	Review and provenance
attributes.comparison.adaptation Thresholds chosen on this dataset for AlphaMissense rows 2-3 and ΔΔG; developer thresholds for AlphaMissense row 1; VCEP thresholds for BayesDel Context-only references	ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence Original source ↗ Table 1, row 5 ('AM' group) Version: American Journal of Human Genetics 112(5):993, published 2025; PMC12120176 full-text XML Retrieved: 2026-10-09T21:18:06Z	not individually reviewed No individual claim review recorded independent paper Audit details Field: `attributes.comparison.adaptation` Source artifact SHA-256: `cd089e7c621818f457f54f93c37cc1b9d535e531212b1aaf431fcbdd733bbda1` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
attributes.comparison.aggregation Pooled over variants Context-only references	ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence Original source ↗ Table 1, row 5 ('AM' group) Version: American Journal of Human Genetics 112(5):993, published 2025; PMC12120176 full-text XML Retrieved: 2026-10-09T21:18:06Z	not individually reviewed No individual claim review recorded independent paper Audit details Field: `attributes.comparison.aggregation` Source artifact SHA-256: `cd089e7c621818f457f54f93c37cc1b9d535e531212b1aaf431fcbdd733bbda1` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
attributes.comparison.budget Not reported Context-only references	ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence Original source ↗ Table 1, row 5 ('AM' group) Version: American Journal of Human Genetics 112(5):993, published 2025; PMC12120176 full-text XML Retrieved: 2026-10-09T21:18:06Z	missing or unspecified No individual claim review recorded independent paper Audit details Field: `attributes.comparison.budget` Source artifact SHA-256: `cd089e7c621818f457f54f93c37cc1b9d535e531212b1aaf431fcbdd733bbda1` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
attributes.comparison.dataset_version Not reported Context-only references	ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence Original source ↗ Table 1, row 5 ('AM' group) Version: American Journal of Human Genetics 112(5):993, published 2025; PMC12120176 full-text XML Retrieved: 2026-10-09T21:18:06Z	missing or unspecified No individual claim review recorded independent paper Audit details Field: `attributes.comparison.dataset_version` Source artifact SHA-256: `cd089e7c621818f457f54f93c37cc1b9d535e531212b1aaf431fcbdd733bbda1` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
attributes.comparison.inputs Missense variant (and structure for ΔΔG) Context-only references	ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence Original source ↗ Table 1, row 5 ('AM' group) Version: American Journal of Human Genetics 112(5):993, published 2025; PMC12120176 full-text XML Retrieved: 2026-10-09T21:18:06Z	not individually reviewed No individual claim review recorded independent paper Audit details Field: `attributes.comparison.inputs` Source artifact SHA-256: `cd089e7c621818f457f54f93c37cc1b9d535e531212b1aaf431fcbdd733bbda1` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
attributes.comparison.metric_implementation Log2 likelihood ratio of LoF versus FUNC within each score range, with 95% CI Context-only references	ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence Original source ↗ Table 1, row 5 ('AM' group) Version: American Journal of Human Genetics 112(5):993, published 2025; PMC12120176 full-text XML Retrieved: 2026-10-09T21:18:06Z	not individually reviewed No individual claim review recorded independent paper Audit details Field: `attributes.comparison.metric_implementation` Source artifact SHA-256: `cd089e7c621818f457f54f93c37cc1b9d535e531212b1aaf431fcbdd733bbda1` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
attributes.comparison.population 1,519 BRCA1 RING and BRCT missense variants: 337 LoF and 1,182 FUNC by MAVE score; 119 intermediate variants excluded Context-only references	ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence Original source ↗ Table 1, row 5 ('AM' group) Version: American Journal of Human Genetics 112(5):993, published 2025; PMC12120176 full-text XML Retrieved: 2026-10-09T21:18:06Z	not individually reviewed No individual claim review recorded independent paper Audit details Field: `attributes.comparison.population` Source artifact SHA-256: `cd089e7c621818f457f54f93c37cc1b9d535e531212b1aaf431fcbdd733bbda1` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
attributes.comparison.protocol_id brca-20261009-protocol-ramadane2025-pp3-bp4 Context-only references	ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence Original source ↗ Table 1, row 5 ('AM' group) Version: American Journal of Human Genetics 112(5):993, published 2025; PMC12120176 full-text XML Retrieved: 2026-10-09T21:18:06Z	not individually reviewed No individual claim review recorded independent paper Audit details Field: `attributes.comparison.protocol_id` Source artifact SHA-256: `cd089e7c621818f457f54f93c37cc1b9d535e531212b1aaf431fcbdd733bbda1` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
attributes.comparison.split Whole dataset Context-only references	ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence Original source ↗ Table 1, row 5 ('AM' group) Version: American Journal of Human Genetics 112(5):993, published 2025; PMC12120176 full-text XML Retrieved: 2026-10-09T21:18:06Z	not individually reviewed No individual claim review recorded independent paper Audit details Field: `attributes.comparison.split` Source artifact SHA-256: `cd089e7c621818f457f54f93c37cc1b9d535e531212b1aaf431fcbdd733bbda1` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact
attributes.origin independent_paper Context-only references	ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence Original source ↗ Table 1, row 5 ('AM' group) Version: American Journal of Human Genetics 112(5):993, published 2025; PMC12120176 full-text XML Retrieved: 2026-10-09T21:18:06Z	not individually reviewed No individual claim review recorded independent paper Audit details Field: `attributes.origin` Source artifact SHA-256: `cd089e7c621818f457f54f93c37cc1b9d535e531212b1aaf431fcbdd733bbda1` Hash scope: Hash scope not separately documented; inspect source record Inspected artifact

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Sources and history

Release 2026-10-10-84341e0b121f · Record review: source checked

1 source records and release history

ACMG/AMP interpretation of BRCA1 missense variants: Structure-informed scores add evidence strength granularity to the PP3/BP4 computational evidence · Original source · American Journal of Human Genetics 112(5):993, published 2025; PMC12120176 full-text XML

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Technical metadata and extraction receipts

Stable ID: brca-20261009-eval-ramadane2025-am-0-65-0-75-pp3-bp4

areas: dna-genomes
contexts: clinical_research
origin: independent_paper
protocol: brca-20261009-protocol-ramadane2025-pp3-bp4
version: Primary source as retrieved 2026-10-09
comparison: protocol id: brca-20261009-protocol-ramadane2025-pp3-bp4; dataset version: Not reported; split: Whole dataset; population: 1,519 BRCA1 RING and BRCT missense variants: 337 LoF and 1,182 FUNC by MAVE score; 119 intermediate variants excluded; inputs: Missense variant (and structure for ΔΔG); adaptation: Thresholds chosen on this dataset for AlphaMissense rows 2-3 and ΔΔG; developer thresholds for AlphaMissense row 1; VCEP thresholds for BayesDel; metric implementation: Log2 likelihood ratio of LoF versus FUNC within each score range, with 95% CI; aggregation: Pooled over variants; budget: Not reported
source locator: Table 1, row 5 ('AM' group)
missing metadata: comparison.dataset version: reason: unreported

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