fitCons (Brandes et al. 2023 clinical benchmarks); dbNSFP 4.3a

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Evaluations and results

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

Sorted by AUPRC (balanced PRC-AUC over the variants both methods score: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot) (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	AUPRC (balanced PRC-AUC over the variants both methods score: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot)	AUPRC (balanced PRC-AUC: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot)	AUROC (global ROC-AUC over all variants; zero-shot)	AUROC (global ROC-AUC over the variants both methods score; zero-shot)
fitCons (Brandes et al. 2023 clinical benchmarks)Evaluation	HGMD/gnomAD missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2), HGMD/gnomAD missense variants scored by both ESM1b and fitCons (Brandes et al. 2023)	0.546 (best in column)	Not reported	Not reported	0.565 (best in column)
fitCons (Brandes et al. 2023 clinical benchmarks)Evaluation	ClinVar missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2), ClinVar missense variants scored by both ESM1b and fitCons (Brandes et al. 2023)	0.512	Not reported	Not reported	0.515
fitCons (Brandes et al. 2023 clinical benchmarks)Evaluation	ClinVar missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2), ClinVar missense pathogenic vs benign, primary isoforms (Brandes et al. 2023, from the EVE portal)	Not reported	0.512 (best in column)	0.529 (best in column)	Not reported
fitCons (Brandes et al. 2023 clinical benchmarks)Evaluation	HGMD/gnomAD missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2), HGMD disease-causing vs gnomAD common missense variants, primary isoforms (Brandes et al. 2023)	Not reported	0.477	0.468	Not reported

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Exact evaluated configurations and original reported results
Tested configuration	Protocol and dataset	Finding	Evidence and details
Configuration: fitCons (Brandes et al. 2023 clinical benchmarks)	Protocol: ClinVar missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2) Dataset: ClinVar missense pathogenic vs benign, primary isoforms (Brandes et al. 2023, from the EVE portal)	0.512 AUPRC (balanced PRC-AUC: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source fitCons on ClinVar missense, variants scored by all 19 methods (Brandes et al. 2023) gfm-guides-20261014-esm1b-protocol-clinvar-all-19-methods Aggregation: Not reported Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods · Supplementary Table 2 sheet 'Table_of_results_ClinVar' cell C20, row 'fitCons', column 'AUC_Balanced_AUPRC'
Configuration: fitCons (Brandes et al. 2023 clinical benchmarks)	Protocol: ClinVar missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2) Dataset: ClinVar missense pathogenic vs benign, primary isoforms (Brandes et al. 2023, from the EVE portal)	0.529 AUROC (global ROC-AUC over all variants; zero-shot) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source fitCons on ClinVar missense, variants scored by all 19 methods (Brandes et al. 2023) gfm-guides-20261014-esm1b-protocol-clinvar-all-19-methods Aggregation: Not reported Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods · Supplementary Table 2 sheet 'Table_of_results_ClinVar' cell B20, row 'fitCons', column 'AUC_AUROC'
Configuration: fitCons (Brandes et al. 2023 clinical benchmarks)	Protocol: ClinVar missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2) Dataset subset: ClinVar missense variants scored by both ESM1b and fitCons (Brandes et al. 2023)	0.512 AUPRC (balanced PRC-AUC over the variants both methods score: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source fitCons on ClinVar missense, head to head against ESM1b (Brandes et al. 2023) gfm-guides-20261014-esm1b-protocol-clinvar-head-to-head Aggregation: Not reported Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods · Supplementary Table 2 sheet 'Table_of_results_ClinVar' cell G20, row 'fitCons', column 'head2head_VEP_auc_Balanced_AUPRC'
Configuration: fitCons (Brandes et al. 2023 clinical benchmarks)	Protocol: ClinVar missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2) Dataset subset: ClinVar missense variants scored by both ESM1b and fitCons (Brandes et al. 2023)	0.515 AUROC (global ROC-AUC over the variants both methods score; zero-shot) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source fitCons on ClinVar missense, head to head against ESM1b (Brandes et al. 2023) gfm-guides-20261014-esm1b-protocol-clinvar-head-to-head Aggregation: Not reported Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods · Supplementary Table 2 sheet 'Table_of_results_ClinVar' cell E20, row 'fitCons', column 'head2head_VEP_auc_AUROC'
Configuration: fitCons (Brandes et al. 2023 clinical benchmarks)	Protocol: HGMD/gnomAD missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2) Dataset: HGMD disease-causing vs gnomAD common missense variants, primary isoforms (Brandes et al. 2023)	0.477 AUPRC (balanced PRC-AUC: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source fitCons on HGMD/gnomAD missense, variants scored by all 19 methods (Brandes et al. 2023) gfm-guides-20261014-esm1b-protocol-hgmd-all-19-methods Aggregation: Not reported Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods · Supplementary Table 2 sheet 'Table_of_results_HGMD' cell C20, row 'fitCons', column 'AUC_Balanced_AUPRC'
Configuration: fitCons (Brandes et al. 2023 clinical benchmarks)	Protocol: HGMD/gnomAD missense pathogenicity, variants scored by all 19 eligible methods (Brandes et al. 2023 Fig. 2e-f, Supplementary Table 2) Dataset: HGMD disease-causing vs gnomAD common missense variants, primary isoforms (Brandes et al. 2023)	0.468 AUROC (global ROC-AUC over all variants; zero-shot) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source fitCons on HGMD/gnomAD missense, variants scored by all 19 methods (Brandes et al. 2023) gfm-guides-20261014-esm1b-protocol-hgmd-all-19-methods Aggregation: Not reported Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods · Supplementary Table 2 sheet 'Table_of_results_HGMD' cell B20, row 'fitCons', column 'AUC_AUROC'
Configuration: fitCons (Brandes et al. 2023 clinical benchmarks)	Protocol: HGMD/gnomAD missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2) Dataset subset: HGMD/gnomAD missense variants scored by both ESM1b and fitCons (Brandes et al. 2023)	0.546 AUPRC (balanced PRC-AUC over the variants both methods score: mean over 100 random downsamples to equal pathogenic and benign counts (80% of the minority class); zero-shot) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source fitCons on HGMD/gnomAD missense, head to head against ESM1b (Brandes et al. 2023) gfm-guides-20261014-esm1b-protocol-hgmd-head-to-head Aggregation: Not reported Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods · Supplementary Table 2 sheet 'Table_of_results_HGMD' cell G20, row 'fitCons', column 'head2head_VEP_auc_Balanced_AUPRC'
Configuration: fitCons (Brandes et al. 2023 clinical benchmarks)	Protocol: HGMD/gnomAD missense pathogenicity, ESM1b head to head with one other method on the variants both score (Brandes et al. 2023 Fig. 2g,h, Supplementary Table 2) Dataset subset: HGMD/gnomAD missense variants scored by both ESM1b and fitCons (Brandes et al. 2023)	0.565 AUROC (global ROC-AUC over the variants both methods score; zero-shot) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Independent external evaluation · Source checked Methods, coverage and source fitCons on HGMD/gnomAD missense, head to head against ESM1b (Brandes et al. 2023) gfm-guides-20261014-esm1b-protocol-hgmd-head-to-head Aggregation: Not reported Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods · Supplementary Table 2 sheet 'Table_of_results_HGMD' cell E20, row 'fitCons', column 'head2head_VEP_auc_AUROC'

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Release 2026-10-22-1b7cf027e4f6 · Record review: source checked

2 source records and release history

Genome-wide prediction of disease variant effects with a deep protein language model (Brandes et al., Nature Genetics 2023) · Original source · Version of record, Nature Genetics 55, 1512-1522 (published 2023-08-10)
Brandes et al. 2023 Supplementary Table 2: full benchmark evaluations of ESM1b and all other methods · Original source · Version of record, Nature Genetics 55, 1512-1522 (published 2023-08-10)

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Technical metadata and extraction receipts

Stable ID: gfm-guides-20261014-esm1b-config-fitcons

areas: dna-genomes
contexts: clinical_research
method types: specialist
reported name: fitCons
version: dbNSFP 4.3a
parameters: dbNSFP 4.3a score; the three cell-line fitCons versions were excluded, so this is taken to be integrated fitCons
foundation model eligible: false
source locator: Supplementary Table 2 column vep_name 'fitCons'; Methods 'ESM1b' and 'Other VEP methods'
provenance note: fitCons as scored in the Brandes et al. 2023 clinical missense benchmarks.

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