Protocol

BRCA1 MAVE PP3/BP4 evidence strength by score threshold (Ramadane-Morchadi et al. 2025 Table 1)

Log2 likelihood ratio for BP4 and PP3 score ranges and the share of variants left with no computational code, for AlphaMissense, FoldX ΔΔG and BayesDel.

8 evaluations · 24 results

Overview

Log2 likelihood ratio for BP4 and PP3 score ranges and the share of variants left with no computational code, for AlphaMissense, FoldX ΔΔG and BayesDel.

Consult the linked sources for architecture or protocol details. Missing evidence is not evidence of a missing capability.

8 recorded evaluations, 24 metric rows. A comparison chart has not yet been validated for these results. The table retains the individual findings and their sources.

View coverage and remaining gaps across all benchmarks

Results

Results are available, but no reviewed comparison panel is linked in this release.

All evaluations

8 evaluations · 24 results. Different protocols are not a single leaderboard.

Filter evaluations

Tested model or methodProtocolDatasetEvaluation setupMetricEvidence origin

Applied filters: All linked evaluations

Exact evaluated configurations and original reported results
Tested configuration	Protocol and dataset	Finding	Evidence and details
Configuration: AlphaMissense, BP4 ≤0.34 and PP3 ≥0.56 (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	−4.603 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -5.535 to -3.671 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense, BP4 ≤0.34 and PP3 ≥0.56, 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 3 ('AM' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)'
Configuration: AlphaMissense, BP4 ≤0.34 and PP3 ≥0.56 (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	12% 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 ≤0.34 and PP3 ≥0.56, 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 3 ('AM' group), column 'No bioinformatic code applicable'
Configuration: AlphaMissense, BP4 ≤0.34 and PP3 ≥0.56 (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	2.08 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 1.919 to 2.247 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense, BP4 ≤0.34 and PP3 ≥0.56, 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 3 ('AM' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)'
Configuration: AlphaMissense, BP4 ≤0.60 and PP3 ≥0.80 (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	−3.038 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -3.508 to -2.569 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense, BP4 ≤0.60 and PP3 ≥0.80, 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 4 ('AM' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)'
Configuration: AlphaMissense, BP4 ≤0.60 and PP3 ≥0.80 (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	10% 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 ≤0.60 and PP3 ≥0.80, 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 4 ('AM' group), column 'No bioinformatic code applicable'
Configuration: AlphaMissense, BP4 ≤0.60 and PP3 ≥0.80 (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	3.01 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.746 to 3.269 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense, BP4 ≤0.60 and PP3 ≥0.80, 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 4 ('AM' group), column 'Pathogenicity evidence (PP3): 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	−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)'
Configuration: BayesDel, BP4 ≤0.15 and PP3 ≥0.28 (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	−2.923 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -3.401 to -2.444 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source BayesDel, BP4 ≤0.15 and PP3 ≥0.28, 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 10 ('BD' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)'
Configuration: BayesDel, BP4 ≤0.15 and PP3 ≥0.28 (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	14% 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 BayesDel, BP4 ≤0.15 and PP3 ≥0.28, 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 10 ('BD' group), column 'No bioinformatic code applicable'
Configuration: BayesDel, BP4 ≤0.15 and PP3 ≥0.28 (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	2.64 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.415 to 2.872 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source BayesDel, BP4 ≤0.15 and PP3 ≥0.28, 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 10 ('BD' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)'
Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0 (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	−3.417 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -4.051 to -2.784 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0, 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 6 ('ΔΔG AF b' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)'
Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0 (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	26% 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 FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0, 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 6 ('ΔΔG AF b' group), column 'No bioinformatic code applicable'
Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0 (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	2.69 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.448 to 2.933 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.0 and PP3 ≥+3.0, 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 6 ('ΔΔG AF b' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)'
Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.5 and PP3 ≥+2.5 (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	−2.946 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -3.433 to -2.456 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.5 and PP3 ≥+2.5, 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 7 ('ΔΔG AF b' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)'
Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.5 and PP3 ≥+2.5 (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	8% 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 FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.5 and PP3 ≥+2.5, 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 7 ('ΔΔG AF b' group), column 'No bioinformatic code applicable'
Configuration: FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.5 and PP3 ≥+2.5 (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	2.37 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.164 to 2.570 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source FoldX5.0 ΔΔG on AlphaFold2 models, BP4 ≤+1.5 and PP3 ≥+2.5, 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 7 ('ΔΔG AF b' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)'
Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.0 and PP3 ≥+3.0 (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	−2.663 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -3.135 to -2.191 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.0 and PP3 ≥+3.0, 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 8 ('ΔΔG PDB b' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)'
Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.0 and PP3 ≥+3.0 (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	26% 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 FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.0 and PP3 ≥+3.0, 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 8 ('ΔΔG PDB b' group), column 'No bioinformatic code applicable'
Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.0 and PP3 ≥+3.0 (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	2.78 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.515 to 3.045 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.0 and PP3 ≥+3.0, 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 8 ('ΔΔG PDB b' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)'
Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5 (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	−2.264 log2-likelihood-ratio unitless · lower Uncertainty: 95% CI -2.632 to -1.895 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5, 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 9 ('ΔΔG PDB b' group), column 'Benignity evidence (BP4): Evidence strength, log 2 LR (95% CI)'
Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5 (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	12% 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 FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5, 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 9 ('ΔΔG PDB b' group), column 'No bioinformatic code applicable'
Configuration: FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5 (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	2.31 log2-likelihood-ratio unitless · higher Uncertainty: 95% CI 2.093 to 2.525 Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5, 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 9 ('ΔΔG PDB b' group), column 'Pathogenicity evidence (PP3): Evidence strength, log 2 LR (95% CI)'

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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-protocol-ramadane2025-pp3-bp4

areas: dna-genomes
contexts: clinical_research
protocol: Variants are assigned BP4, no code, or PP3 by score thresholds; the likelihood ratio of each range for LoF versus FUNC is converted to log2 (Tavtigian points scale: 1, 2 and 4 are supporting, moderate and strong).
version: Table 1
metric: log2-likelihood-ratio
limitations: LoF and FUNC functional classes (Findlay et al. 2018 saturation genome editing) stand in for pathogenic and benign; 119 intermediate variants are excluded.; The AlphaMissense 0.65/0.75 and ΔΔG 1.5/2.5 thresholds were chosen by a trade-off process on the same 1,519 variants (Results), so those rows are not held-out estimates; the 0.60/0.80 and 1.0/3.0 alternatives are shown alongside without a stated origin. The AlphaMissense 0.34/0.56 thresholds are the developers' and the BayesDel 0.15/0.28 thresholds are the BRCA1 VCEP's.; The BRCA1 VCEP BayesDel thresholds were calibrated by ENIGMA on functional reference labels in the same domains (existing ENIGMA judgements); overlap with this dataset is possible but not stated.; BRCA1 RING and BRCT domains only.; Three authors are employees of Ambry Genetics, a commercial testing laboratory (Declaration of interests); none of the compared tools is from the authors.; The same saturation genome editing data are the BRCA1 truth set in Cubuk et al. 2021; agreement between these studies is not independent replication.; Log2 likelihood ratios come from an online calculator (gwiggins.shinyapps.io/lr_shiny); the interval method is not stated beyond 95% CI.; Log2 likelihood ratios for BP4 ranges are negative (lower favours benignity) and for PP3 ranges positive; they are not on the same scale as the likelihood-ratio rows of Cubuk et al.
denominator: 1519
source locator: Table 1; Material and methods paragraph 4; Results paragraphs 8-12

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