Configuration

ESM1b 650M log-likelihood ratio, Brandes et al. pipeline (Lu et al. 2025)

ESM1b esm1b_t33_650M_UR50S scoring missense variants by the logit difference between alternative and reference residues, with 1,022-residue sliding windows; stop-gains scored by the most deleterious downstream missense score.

5 evaluations · 5 results 12 open disagreements between studies involve its model

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Evaluations and results

5 evaluations · 5 results. Different protocols are not a single leaderboard.

Protocol: ClinVar pathogenic versus benign SNVs within variant type, AUROC (Lu et al. 2025)

Sorted by AUROC (ClinVar pathogenic vs benign SNVs, Missense & 3'UTR) (higher is better). The best value in each column is highlighted. Decimals are rounded for display; each value links to the printed value and its source.

Tested configuration	Protocol and dataset	AUROC (ClinVar pathogenic vs benign SNVs, Missense & 3'UTR)	AUROC (ClinVar pathogenic vs benign SNVs, Missense & Intron (Non-splice))	AUROC (ClinVar pathogenic vs benign SNVs, Missense)	AUROC (ClinVar pathogenic vs benign SNVs, Start loss)	AUROC (ClinVar pathogenic vs benign SNVs, Stop gain)
ESM1b 650M log-likelihood ratio, Brandes et al. pipeline (Lu et al. 2025)Evaluation	Lu et al. 2025 ClinVar benchmark: Missense & 3'UTR (Figure 1)	0.906	Not reported	Not reported	Not reported	Not reported
ESM1b 650M log-likelihood ratio, Brandes et al. pipeline (Lu et al. 2025)Evaluation	Lu et al. 2025 ClinVar benchmark: Missense & Intron (Non-splice) (Figure 1)	Not reported	0.8	Not reported	Not reported	Not reported
ESM1b 650M log-likelihood ratio, Brandes et al. pipeline (Lu et al. 2025)Evaluation	Lu et al. 2025 ClinVar benchmark: Missense (Figure 1)	Not reported	Not reported	0.919	Not reported	Not reported
ESM1b 650M log-likelihood ratio, Brandes et al. pipeline (Lu et al. 2025)Evaluation	Lu et al. 2025 ClinVar benchmark: Start loss (Figure 1)	Not reported	Not reported	Not reported	0.681	Not reported
ESM1b 650M log-likelihood ratio, Brandes et al. pipeline (Lu et al. 2025)Evaluation	Lu et al. 2025 ClinVar benchmark: Stop gain (Figure 1)	Not reported	Not reported	Not reported	Not reported	0.788

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Tested configuration	Protocol and dataset	Finding	Evidence and details
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: 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 & 3'UTR (Figure 1)	0.906 AUROC (ClinVar pathogenic vs benign SNVs, Missense & 3'UTR) 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 & 3'UTR 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 3 'Missense & 3'UTR (N=117, %P=40.97%)', row 'ESM1b', 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 (Figure 1)	0.919 AUROC (ClinVar pathogenic vs benign SNVs, Missense) 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 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 1 'Missense (N=50,820, %P=40.09%)', row 'ESM1b', 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: Start loss (Figure 1)	0.681 AUROC (ClinVar pathogenic vs benign SNVs, Start loss) 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 Start loss 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 2, panel 5 'Start loss (N=847, %P=97.53%)', row 'ESM1b', 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: Stop gain (Figure 1)	0.788 AUROC (ClinVar pathogenic vs benign SNVs, Stop gain) 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 Stop gain 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 4 'Stop gain (N=42,408, %P=98.13%)', row 'ESM1b', bar label

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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-config-esm1b-llr

areas: dna-genomes
contexts: clinical_research
method types: foundation_model
reported name: ESM1b
parameters: esm1b_t33_650M_UR50S; 1,022 aa context, windows with >511 aa overlap combined by weighted sum; start-loss treated as missense; stop-gain = most deleterious possible missense between the stop and the protein end.
source locator: Methods 'ESM models' and 'Scoring stop-gain variants by protein models' (page 15)

Related records

configuration of: ESM-1b
system: ESM1b on ClinVar Missense & Intron (Non-splice) SNVs (Lu et al. 2025 Figure 1)
system: ESM1b on ClinVar Missense & 3'UTR SNVs (Lu et al. 2025 Figure 1)
system: ESM1b on ClinVar Missense SNVs (Lu et al. 2025 Figure 1)
system: ESM1b on ClinVar Start loss SNVs (Lu et al. 2025 Figure 1)
system: ESM1b on ClinVar Stop gain SNVs (Lu et al. 2025 Figure 1)

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