Evaluation

FoldX5.0 ΔΔG on experimental PDB structures, BP4 ≤+1.5 and PP3 ≥+2.5, BRCA1 MAVE evidence strength (Ramadane-Morchadi et al. 2025)

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

Research readiness

These checks assess whether the evidence supports a reproducible investigation. A source-checked score alone does not meet these requirements.

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

Evidence incomplete

Replay metrics

Exact outcomes, predictions, identifiers and evaluator are connected.

Missing or unresolved evidence

No verified artifact manifest is linked to this exact record.
artifact hashes: verification is missing
join integrity: verification is missing
score semantics: verification is missing
metric replay: verification is missing

Verified: Not verified

Evidence incomplete

Investigate discrepancies

Replay evidence includes annotations and an assessment of dependence. Unknown independence permits descriptive analysis only.

Missing or unresolved evidence

No verified artifact manifest is linked to this exact record.
artifact hashes: verification is missing
join integrity: verification is missing
score semantics: verification is missing
metric replay: verification is missing
annotations: verification is missing
dependence: verification is missing

Verified: Not verified

Evidence incomplete

Run locally

A pinned recipe describes the inputs, environment and resource requirements.

Missing or unresolved evidence

No verified artifact manifest is linked to this exact record.
artifact hashes: verification is missing
join integrity: verification is missing
score semantics: verification is missing
recipe pinned: verification is missing
resource estimate: verification is missing

Verified: Not verified

Evidence incomplete

Validate independently

Separate data and exposure records support an independent test.

Missing or unresolved evidence

No verified artifact manifest is linked to this exact record.
artifact hashes: verification is missing
join integrity: verification is missing
score semantics: verification is missing
independent validation: verification is missing
overlap checked: verification is missing

Verified: Not verified

Readiness describes the evidence in this release. Availability on your computer is checked separately when an investigation runs. Existing data exposure can prevent independent validation even when files are available.

Artifacts and reproduction

No verified artifact manifest is connected to this record yet. The gaps above identify what is needed before analysis can begin.

Read reviewed discrepancy investigations

Evaluation results

1 evaluation · 3 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: 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)'

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

Evaluation procedure

brca-20261009-protocol-ramadane2025-pp3-bp4

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

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

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.

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 9 ('ΔΔG PDB b' 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 9 ('ΔΔG PDB b' 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 9 ('ΔΔG PDB b' 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 9 ('ΔΔG PDB b' 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 9 ('ΔΔG PDB b' 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 9 ('ΔΔG PDB b' 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 9 ('ΔΔG PDB b' 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 9 ('ΔΔG PDB b' 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 9 ('ΔΔG PDB b' 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 9 ('ΔΔG PDB b' 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

All evidence (JSONL) (gzip)How to read the evidence

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

Download this release (gzip)

Technical metadata and extraction receipts

Stable ID: brca-20261009-eval-ramadane2025-ddg-pdb-1-5-2-5-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 9 ('ΔΔG PDB b' group)
missing metadata: comparison.dataset version: reason: unreported

Related records

Suggest a correction