Dataset subset

Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)

ClinVar SNVs in the 'Missense & Intron (Non-splice)' group of the Lu et al. 2025 benchmark, restricted to variants scored by every model in the panel.

Evaluation results

12 evaluations · 12 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: AlphaGenome all outputs, quantile, maximum (Lu et al. 2025)	Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025) Dataset subset: Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	0.583 AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice)) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaGenome on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1) lu-hetero-20261019-protocol-clinvar-variant-type-auroc Aggregation: Not reported Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Figure 1 (page 8), column 3, panel 2 'Missense & Intron (Non-splice) (N=255, %P=17.91%)', row 'AlphaGenome', bar label
Configuration: AlphaMissense precomputed scores (Lu et al. 2025)	Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025) Dataset subset: Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	0.924 AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice)) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source AlphaMissense on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1) lu-hetero-20261019-protocol-clinvar-variant-type-auroc Aggregation: Not reported Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Figure 1 (page 8), column 3, panel 2 'Missense & Intron (Non-splice) (N=255, %P=17.91%)', row 'AlphaMissense', bar label
Configuration: DNABERT-2 117M, CLS embedding L2 distance (Lu et al. 2025)	Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025) Dataset subset: Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	0.449 AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice)) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source DNABERT2 on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1) lu-hetero-20261019-protocol-clinvar-variant-type-auroc Aggregation: Not reported Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Figure 1 (page 8), column 3, panel 2 'Missense & Intron (Non-splice) (N=255, %P=17.91%)', row 'DNABERT2', bar label
Configuration: ESM1b 650M log-likelihood ratio, Brandes et al. pipeline (Lu et al. 2025)	Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025) Dataset subset: Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	0.8 AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice)) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source ESM1b on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1) lu-hetero-20261019-protocol-clinvar-variant-type-auroc Aggregation: Not reported Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Figure 1 (page 8), column 3, panel 2 'Missense & Intron (Non-splice) (N=255, %P=17.91%)', row 'ESM1b', bar label
Configuration: ESM1v model 1 log-likelihood ratio, Brandes et al. pipeline (Lu et al. 2025)	Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025) Dataset subset: Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	0.769 AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice)) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source ESM1v on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1) lu-hetero-20261019-protocol-clinvar-variant-type-auroc Aggregation: Not reported Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Figure 1 (page 8), column 3, panel 2 'Missense & Intron (Non-splice) (N=255, %P=17.91%)', row 'ESM1v', bar label
Configuration: ESM2 650M log-likelihood ratio, Brandes et al. pipeline (Lu et al. 2025)	Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025) Dataset subset: Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	0.818 AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice)) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source ESM2 on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1) lu-hetero-20261019-protocol-clinvar-variant-type-auroc Aggregation: Not reported Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Figure 1 (page 8), column 3, panel 2 'Missense & Intron (Non-splice) (N=255, %P=17.91%)', row 'ESM2', bar label
Configuration: Evo 2 7B base, 8,192 bp log-likelihood ratio (Lu et al. 2025)	Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025) Dataset subset: Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	0.835 AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice)) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source Evo2 on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1) lu-hetero-20261019-protocol-clinvar-variant-type-auroc Aggregation: Not reported Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Figure 1 (page 8), column 3, panel 2 'Missense & Intron (Non-splice) (N=255, %P=17.91%)', row 'Evo2', bar label
Configuration: GPN-MSA precomputed hg38 scores (Lu et al. 2025)	Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025) Dataset subset: Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	0.896 AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice)) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source GPN-MSA on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1) lu-hetero-20261019-protocol-clinvar-variant-type-auroc Aggregation: Not reported Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Figure 1 (page 8), column 3, panel 2 'Missense & Intron (Non-splice) (N=255, %P=17.91%)', row 'GPN-MSA', bar label
Configuration: Nucleotide Transformer 2.5B multi-species, CLS embedding L2 distance (Lu et al. 2025)	Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025) Dataset subset: Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	0.664 AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice)) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source Nucleotide Transformer on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1) lu-hetero-20261019-protocol-clinvar-variant-type-auroc Aggregation: Not reported Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Figure 1 (page 8), column 3, panel 2 'Missense & Intron (Non-splice) (N=255, %P=17.91%)', row 'Nucleotide Transformer', bar label
Configuration: PhyloGPN, official example code (Lu et al. 2025)	Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025) Dataset subset: Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	0.689 AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice)) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source PhyloGPN on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1) lu-hetero-20261019-protocol-clinvar-variant-type-auroc Aggregation: Not reported Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Figure 1 (page 8), column 3, panel 2 'Missense & Intron (Non-splice) (N=255, %P=17.91%)', row 'PhyloGPN', bar label
Configuration: PhyloP 100-way vertebrate (Lu et al. 2025)	Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025) Dataset subset: Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	0.868 AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice)) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source PhyloP on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1) lu-hetero-20261019-protocol-clinvar-variant-type-auroc Aggregation: Not reported Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Figure 1 (page 8), column 3, panel 2 'Missense & Intron (Non-splice) (N=255, %P=17.91%)', row 'PhyloP', bar label
Configuration: PrimateAI-3D precomputed scores (Lu et al. 2025)	Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025) Dataset subset: Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	0.905 AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice)) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source PrimateAI-3D on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1) lu-hetero-20261019-protocol-clinvar-variant-type-auroc Aggregation: Not reported Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Figure 1 (page 8), column 3, panel 2 'Missense & Intron (Non-splice) (N=255, %P=17.91%)', row 'PrimateAI-3D', bar label

Source checking is not independent reproduction. Release 2026-11-02-a7f03c9e55a5.

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Release 2026-11-02-a7f03c9e55a5 · Evidence verified: Not verified

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Evidence

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Evidence table

Inspect claims, sources and review details

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6 evidence rows matching the loaded filters

Claims, original sources and review scope · Release 2026-11-02-a7f03c9e55a5
Property and statement	Original source and location	Review and provenance
Original printed counts N=255, %P=17.91% Context-only references	Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) Original source ↗ Figure 1 (page 8), column 3, panel 2, title 'Missense & Intron (Non-splice) (N=255, %P=17.91%)' Version: bioRxiv preprint version 2, posted 2025-09-10 (version 1 posted 2025-09-08); full-text PDF (21 pages) Retrieved: 2026-10-19T12:23:08Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.original_printed_counts` Source artifact SHA-256: `5b8e939257000811a6eaddd90d9de3e03bf1ac0e9015a38769df887ee01f9bf2` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF on each download: a second retrieval at 2026-10-19T12:31:50Z had the same length (1,100,277 bytes), SHA-256 1a1aa1135ad8aa59bdb949bf8df75262eb6feba51b47f49439dbb819c426fbdd, differed in 32 bytes (ModDate) and had an identical pdftotext -layout text layer. Inspected artifact
Source location Figure 1 (page 8), column 3, panel 2, title 'Missense & Intron (Non-splice) (N=255, %P=17.91%)' Context-only references	Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) Original source ↗ Figure 1 (page 8), column 3, panel 2, title 'Missense & Intron (Non-splice) (N=255, %P=17.91%)' Version: bioRxiv preprint version 2, posted 2025-09-10 (version 1 posted 2025-09-08); full-text PDF (21 pages) Retrieved: 2026-10-19T12:23:08Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.source_locator` Source artifact SHA-256: `5b8e939257000811a6eaddd90d9de3e03bf1ac0e9015a38769df887ee01f9bf2` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF on each download: a second retrieval at 2026-10-19T12:31:50Z had the same length (1,100,277 bytes), SHA-256 1a1aa1135ad8aa59bdb949bf8df75262eb6feba51b47f49439dbb819c426fbdd, differed in 32 bytes (ModDate) and had an identical pdftotext -layout text layer. Inspected artifact
Test count 255 Context-only references	Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) Original source ↗ Figure 1 (page 8), column 3, panel 2, title 'Missense & Intron (Non-splice) (N=255, %P=17.91%)' Version: bioRxiv preprint version 2, posted 2025-09-10 (version 1 posted 2025-09-08); full-text PDF (21 pages) Retrieved: 2026-10-19T12:23:08Z	not individually reviewed No individual claim review recorded Audit details Field: `attributes.test_count` Source artifact SHA-256: `5b8e939257000811a6eaddd90d9de3e03bf1ac0e9015a38769df887ee01f9bf2` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF on each download: a second retrieval at 2026-10-19T12:31:50Z had the same length (1,100,277 bytes), SHA-256 1a1aa1135ad8aa59bdb949bf8df75262eb6feba51b47f49439dbb819c426fbdd, differed in 32 bytes (ModDate) and had an identical pdftotext -layout text layer. Inspected artifact
Description ClinVar SNVs in the 'Missense & Intron (Non-splice)' group of the Lu et al. 2025 benchmark, restricted to variants scored by every model in the panel. Context-only references	Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) Original source ↗ Figure 1 (page 8), column 3, panel 2, title 'Missense & Intron (Non-splice) (N=255, %P=17.91%)' Version: bioRxiv preprint version 2, posted 2025-09-10 (version 1 posted 2025-09-08); full-text PDF (21 pages) Retrieved: 2026-10-19T12:23:08Z	not individually reviewed No individual claim review recorded Audit details Field: `description` Source artifact SHA-256: `5b8e939257000811a6eaddd90d9de3e03bf1ac0e9015a38769df887ee01f9bf2` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF on each download: a second retrieval at 2026-10-19T12:31:50Z had the same length (1,100,277 bytes), SHA-256 1a1aa1135ad8aa59bdb949bf8df75262eb6feba51b47f49439dbb819c426fbdd, differed in 32 bytes (ModDate) and had an identical pdftotext -layout text layer. Inspected artifact
Relationship: used in lu-hetero-20261019-protocol-clinvar-variant-type-auroc Context-only references	Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) Original source ↗ Figure 1 (page 8), column 3, panel 2, title 'Missense & Intron (Non-splice) (N=255, %P=17.91%)' Version: bioRxiv preprint version 2, posted 2025-09-10 (version 1 posted 2025-09-08); full-text PDF (21 pages) Retrieved: 2026-10-19T12:23:08Z	not individually reviewed No individual claim review recorded Audit details Field: `links:used_in:lu-hetero-20261019-protocol-clinvar-variant-type-auroc` Source artifact SHA-256: `5b8e939257000811a6eaddd90d9de3e03bf1ac0e9015a38769df887ee01f9bf2` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF on each download: a second retrieval at 2026-10-19T12:31:50Z had the same length (1,100,277 bytes), SHA-256 1a1aa1135ad8aa59bdb949bf8df75262eb6feba51b47f49439dbb819c426fbdd, differed in 32 bytes (ModDate) and had an identical pdftotext -layout text layer. Inspected artifact
Name Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1) Context-only references	Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) Original source ↗ Figure 1 (page 8), column 3, panel 2, title 'Missense & Intron (Non-splice) (N=255, %P=17.91%)' Version: bioRxiv preprint version 2, posted 2025-09-10 (version 1 posted 2025-09-08); full-text PDF (21 pages) Retrieved: 2026-10-19T12:23:08Z	not individually reviewed No individual claim review recorded Audit details Field: `name` Source artifact SHA-256: `5b8e939257000811a6eaddd90d9de3e03bf1ac0e9015a38769df887ee01f9bf2` Hash scope: SHA-256 of one retrieval of the bioRxiv PDF. bioRxiv stamps the PDF on each download: a second retrieval at 2026-10-19T12:31:50Z had the same length (1,100,277 bytes), SHA-256 1a1aa1135ad8aa59bdb949bf8df75262eb6feba51b47f49439dbb819c426fbdd, differed in 32 bytes (ModDate) and had an identical pdftotext -layout text layer. Inspected artifact

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Sources and history

Release 2026-11-02-a7f03c9e55a5 · Record review: source checked

1 source record and release history

Genomic heterogeneity inflates the performance of variant pathogenicity predictions (Lu, Liu, Lin and Brandes, bioRxiv 2025, v2) · Original source · bioRxiv preprint version 2, posted 2025-09-10 (version 1 posted 2025-09-08); full-text PDF (21 pages)

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Technical metadata and extraction receipts

Stable ID: lu-hetero-20261019-subset-missense-and-intron

areas: dna-genomes
contexts: clinical_research
test count: 255
original printed counts: N=255, %P=17.91%
source locator: Figure 1 (page 8), column 3, panel 2, title 'Missense & Intron (Non-splice) (N=255, %P=17.91%)'

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