Protocol

Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1)

Zero-shot classification of pathogenic/likely pathogenic versus benign/likely benign variants in the ClinVar noncoding SNVs, poorly conserved stratum, AUROC and AUPRC.

15 evaluations · 30 results

Overview

An explanatory profile has not yet been reviewed for this record.

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

15 recorded evaluations, 30 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

15 evaluations · 30 results. Different protocols are not a single leaderboard.

Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) · Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)

Sorted by AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) (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	AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved)	AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved)
SpliceAI (Evo 2 paper variant effect evaluations)Evaluation	0.856 (best in column)	0.966 (best in column)
Pangolin (Evo 2 paper variant effect evaluations)Evaluation	0.666	0.933
CADD (Evo 2 paper variant effect evaluations)Evaluation	0.607	0.908
Evo 2 40B base (Evo 2 paper variant effect evaluations)Evaluation	0.567	0.894
Evo 2 40B (Evo 2 paper variant effect evaluations)Evaluation	0.554	0.897
Evo 2 7B (Evo 2 paper variant effect evaluations)Evaluation	0.525	0.874
Evo 2 7B base (Evo 2 paper variant effect evaluations)Evaluation	0.519	0.874
PhyloP 447 (Evo 2 paper variant effect evaluations)Evaluation	0.165	0.716
PhyloP 241 (Evo 2 paper variant effect evaluations)Evaluation	0.153	0.694
PhyloP 470 (Evo 2 paper variant effect evaluations)Evaluation	0.149	0.68
GPN-MSA (Evo 2 paper variant effect evaluations)Evaluation	0.13	0.706
RNA-FM (Evo 2 paper variant effect evaluations)Evaluation	0.031	0.574
PhyloP 100 (Evo 2 paper variant effect evaluations)Evaluation	0.026	0.547
NT (Evo 2 paper variant effect evaluations)Evaluation	0.023	0.502
Evo 1 (Evo 2 paper variant effect evaluations)Evaluation	0.022	0.527

All 30 result rows with coverage, uncertainty and sources

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: CADD (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.607 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source CADD on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J445, row 445: Model 'CADD', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'
Configuration: CADD (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.908 AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source CADD on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I445, row 445: Model 'CADD', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUROC'
Configuration: Evo 1 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.022 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 1 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J456, row 456: Model 'Evo 1', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'
Configuration: Evo 1 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.527 AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 1 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I456, row 456: Model 'Evo 1', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUROC'
Configuration: Evo 2 40B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.567 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 40B base on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J447, row 447: Model 'Evo 2 40B base', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'
Configuration: Evo 2 40B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.894 AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 40B base on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I447, row 447: Model 'Evo 2 40B base', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUROC'
Configuration: Evo 2 40B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.554 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 40B on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J446, row 446: Model 'Evo 2 40B', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'
Configuration: Evo 2 40B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.897 AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 40B on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I446, row 446: Model 'Evo 2 40B', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUROC'
Configuration: Evo 2 7B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.519 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 7B base on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J449, row 449: Model 'Evo 2 7B base', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'
Configuration: Evo 2 7B base (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.874 AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 7B base on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I449, row 449: Model 'Evo 2 7B base', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUROC'
Configuration: Evo 2 7B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.525 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 7B on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J448, row 448: Model 'Evo 2 7B', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'
Configuration: Evo 2 7B (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.874 AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Evo 2 7B on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I448, row 448: Model 'Evo 2 7B', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUROC'
Configuration: GPN-MSA (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.13 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source GPN-MSA on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J451, row 451: Model 'GPN-MSA', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'
Configuration: GPN-MSA (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.706 AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source GPN-MSA on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I451, row 451: Model 'GPN-MSA', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUROC'
Configuration: NT (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.023 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source NT on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J457, row 457: Model 'NT', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'
Configuration: NT (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.502 AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source NT on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I457, row 457: Model 'NT', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUROC'
Configuration: Pangolin (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.666 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Pangolin on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J444, row 444: Model 'Pangolin', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'
Configuration: Pangolin (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.933 AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source Pangolin on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I444, row 444: Model 'Pangolin', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUROC'
Configuration: PhyloP 100 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.026 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source PhyloP 100 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J455, row 455: Model 'PhyloP 100', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'
Configuration: PhyloP 100 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.547 AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source PhyloP 100 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I455, row 455: Model 'PhyloP 100', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUROC'
Configuration: PhyloP 241 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.153 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source PhyloP 241 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J452, row 452: Model 'PhyloP 241', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'
Configuration: PhyloP 241 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.694 AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source PhyloP 241 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I452, row 452: Model 'PhyloP 241', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUROC'
Configuration: PhyloP 447 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.165 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source PhyloP 447 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J450, row 450: Model 'PhyloP 447', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'
Configuration: PhyloP 447 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.716 AUROC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source PhyloP 447 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell I450, row 450: Model 'PhyloP 447', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUROC'
Configuration: PhyloP 470 (Evo 2 paper variant effect evaluations)	Protocol: Zero-shot ClinVar noncoding SNVs, poorly conserved classification (Evo 2 paper, Supplementary Data 1) Dataset: ClinVar October 2024 release, filtered (Brixi et al. 2026)	0.149 AUPRC (zero-shot; ClinVar noncoding SNVs, poorly conserved) unitless · higher Uncertainty: Not reported by the source Coverage: Not reported scored / Not reported eligible	Author-reported evaluation · Source checked Methods, coverage and source PhyloP 470 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper) gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved Aggregation: Not reported Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026); Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Supplementary Data 1 (sheet 'Sheet1') cell J453, row 453: Model 'PhyloP 470', Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved', column 'AUPRC'

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Reference methods help show what a model adds beyond simple controls. We track a null control and a conventional method for each protocol.

0 of 2 active baseline roles have published Rewire measurements in this release. Measurements on a selected protocol do not establish coverage of an entire suite.

No execution recipe linked to this protocol. Recipe availability does not establish a completed evaluation.

Author-reported evaluations: 15

Literature evidence is not a Rewire measurement. Executed but unpublished runs and private review status are not included.

Null control

Proposed control: requires review

Protocol-valid seeded random ranking; no fitting on assay labels

Protocol-specific applicability, permitted inputs, access, split, evaluator and execution requirements need review before implementation or execution.

This is a suggested selection rule, not a validated method or a measured score.

Conventional reference

Proposed control: requires review

Established label-free reference with explicitly permitted sequence/MSA inputs

Protocol-specific applicability, permitted inputs, access, split, evaluator and execution requirements need review before implementation or execution.

This is a suggested selection rule, not a validated method or a measured score.

Protocol coverage CSV (gzip) · Model evaluation matrix (gzip) · Source table (gzip) · Release and checksums (gzip)

Coverage is derived from release 2026-10-22-1b7cf027e4f6. Source citations describe the original records; they do not validate an unreviewed baseline proposal. No results have been generated by this audit.

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Strengths, limitations and unresolved questions

Evidence

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Evidence table

Inspect claims, sources and review details

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Claims, original sources and review scope · Release 2026-10-22-1b7cf027e4f6
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Sources and history

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

3 source records and release history

evo2: Journal full-text XML · Original source · Retrieved page snapshot; no immutable publisher revision supplied
Genome modelling and design across all domains of life with Evo 2: Supplementary Information (Nature 2026) · Original source · Nature 652 (2026), published 2026-03-04; Supplementary Information file 41586_2026_10176_MOESM1_ESM.pdf (73 pages)
Genome modelling and design across all domains of life with Evo 2: Supplementary Data 1, human variant effect prediction results (Nature 2026) · Original source · Nature 652 (2026), published 2026-03-04; Supplementary Data 1 file 41586_2026_10176_MOESM3_ESM.xlsx

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Technical metadata and extraction receipts

Stable ID: gfm-guides-20261014-evo2-brixi2026-protocol-clinvar-noncoding-snv-poorly-conserved

areas: dna-genomes
contexts: research
protocol: Score each variant zero-shot (for Evo 2, the log-likelihood of the variant sequence minus that of the reference over an 8,192-bp genomic window around the variant) and compute AUROC and AUPRC for pathogenic/likely pathogenic versus benign/likely benign variants in the stratum Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved'.
version: As published, Nature 652 (2026), Supplementary Data 1
source locator: Supplementary Data 1 rows with Data 'ClinVar', Genomic_Feature 'Noncoding', Variant_Type 'SNV', Sub_category 'Poorly conserved'; SI A.3.12 and A.3.13 (page 13); Extended Data Fig. 4
limitations: Positives: 129 pathogenic/likely pathogenic; negatives: 5437 benign/likely benign; total 5566 variants (Supplementary Data 1).; Label 'Poorly conserved'; SI A.3.13 names its bins 'weakly conserved' (0 <= phyloP < 0.5) and 'accelerated evolution' (phyloP < 0); the mapping is not stated.; No split: every model scores the same variants zero-shot (SI A.3.12: 'For each benchmark, we score the same variants with all models').; Supervised comparators (AlphaMissense, CADD, SpliceAI, Pangolin) may have been trained on overlapping variants; training overlap is not reported.; No uncertainty is reported.

Related records

part of: Evo 2 paper zero-shot human variant effect evaluations (Brixi et al. 2026)
uses data: ClinVar October 2024 release, filtered (Brixi et al. 2026)
assessment: CADD on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: Evo 1 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: Evo 2 40B base on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: Evo 2 40B on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: Evo 2 7B base on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: Evo 2 7B on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: GPN-MSA on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: NT on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: Pangolin on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: PhyloP 100 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: PhyloP 241 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: PhyloP 447 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: PhyloP 470 on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: RNA-FM on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)
assessment: SpliceAI on ClinVar noncoding SNVs, poorly conserved (Evo 2 paper)

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