EVC2 p.Ser1161=
c.3483G>A · rs374038474 · VCV508105
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0428%, afr)
Conditions
2
acrofacial dysostosis, Weyers type
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -9.3 | GERP -3.7 |
| Overall | ||
| CADD | 0.375 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0428%
African / African-American · 32/74,792 alleles
Filtering AF
0.0311%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0271%
Overall
0.00546%
87/1,593,034 alleles · ultra-rare
exomes 68/1,441,132 · genomes 19/151,902 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0428% | 2,337 |
| Middle Eastern | 0.0217% | 4,608 |
| South Asian | 0.0103% | 9,711 |
| Remaining individualsnot grpmax-eligible | 0.00969% | 10,325 |
| European (non-Finnish) | 0.00323% | 30,938 |
| Admixed American | 0.00172% | 58,230 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- EVC2
- Protein
- p.Ser1161=
- Coding
- c.3483G>A
- MANE Select
- NM_147127
- dbSNP
- rs374038474
- Type
- single nucleotide variant
- Location
- chr4:5568518 (GRCh38)
- Gene constraint
- LOEUF 1.092 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.33
Similar variants
- EVC2 p.Ser1161Leu Uncertain significance ★★ ⚠ same residue
- EVC2 c.2046+1G>A Likely pathogenic ★★ same condition
- EVC2 c.2047-2A>G Likely pathogenic ★★ same condition
- EVC2 c.229-1G>T Likely pathogenic ★★ same condition
- EVC2 c.229-2A>G Likely pathogenic ★★ same condition
- EVC2 c.3360+1G>A Pathogenic ★★ same condition
- EVC2 c.3659+2T>C Pathogenic/Likely pathogenic ★★ same condition
- EVC2 c.450+2T>C Likely pathogenic ★★ same condition
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/evc2-p-ser1161 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown