EVC p.Val178=
c.534C>A · rs774703104 · VCV779718
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
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 0.46 | GERP -2.1, phastCons 0.048 |
| Overall | ||
| CADD | 5.422 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.00596%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00549%
Overall
0.00576%
93/1,614,024 alleles · ultra-rare
exomes 83/1,461,892 · genomes 10/152,132 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| European (non-Finnish) | 0.0072% | 13,883 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| Admixed American | 0.00333% | 30,000 |
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
- EVC
- Protein
- p.Val178=
- Coding
- c.534C>A
- MANE Select
- NM_153717
- dbSNP
- rs774703104
- Type
- single nucleotide variant
- Location
- chr4:5731574 (GRCh38)
- Gene constraint
- LOEUF 1.134 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.49
- Residue 178
- the 'disordered' region
Similar variants
- EVC p.Val178Ile Likely benign ★★ same residue
- EVC c.1098+1G>A Pathogenic/Likely pathogenic ★★ same condition
- EVC c.175-2A>G Pathogenic/Likely pathogenic ★★ same condition
- EVC c.1777-1G>A Pathogenic/Likely pathogenic ★★ same condition
- EVC c.1777-2A>G Pathogenic/Likely pathogenic ★★ same condition
- EVC c.1886+1G>C Likely pathogenic ★★ same condition
- EVC c.1886+5G>A Pathogenic ★★ same condition
- EVC c.1886+5G>T Pathogenic/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/evc-p-val178 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown