EVC p.Arg371Ser
c.1113G>T · VCV3373675
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.5816 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5816 | likely pathogenic · top 8% in EVC |
|---|---|---|
| REVEL | 0.363 | indeterminate |
| SaProt | LLR -4.02 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.064 | GERP -3.7, phastCons 0.044 |
| Regional constraint | o/e 1.12 | unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic |
| Overall | ||
| CADD | 14.89 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- EVC
- Protein
- p.Arg371Ser
- Coding
- c.1113G>T
- MANE Select
- NM_153717
- Type
- single nucleotide variant
- Location
- chr4:5752850 (GRCh38)
- Gene constraint
- LOEUF 1.134 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.49
Similar variants
- EVC p.Arg371= Likely benign ★ same residue
- EVC c.1098+1G>A Pathogenic/Likely pathogenic ★★ same type
- EVC c.175-2A>G Pathogenic/Likely pathogenic ★★ same type
- EVC c.1777-1G>A Pathogenic/Likely pathogenic ★★ same type
- EVC c.1777-2A>G Pathogenic/Likely pathogenic ★★ same type
- EVC c.1886+1G>C Likely pathogenic ★★ same type
- EVC c.1886+5G>A Pathogenic ★★ same type
- EVC c.1886+5G>T Pathogenic/Likely pathogenic ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/evc-p-arg371ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown