EVC p.Ser286=
c.858G>A · rs752988350 · VCV1096973
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0356%, eas)
Conditions
2
Ellis-van Creveld syndrome
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 2.9 | GERP -1, phastCons 1 |
| Overall | ||
| CADD | 12.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0356%
East Asian · 16/44,882 alleles
Filtering AF
0.0223%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0182%
Overall
0.00217%
35/1,613,836 alleles · ultra-rare
exomes 33/1,461,774 · genomes 2/152,062 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0356% | 2,805 |
| Middle Eastern | 0.0329% | 3,042 |
| Admixed American | 0.005% | 20,000 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| African / African-American | 0.00134% | 74,856 |
| South Asian | 0.0011% | 91,086 |
| European (non-Finnish) | 0.000932% | 107,266 |
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.Ser286=
- Coding
- c.858G>A
- MANE Select
- NM_153717
- dbSNP
- rs752988350
- Type
- single nucleotide variant
- Location
- chr4:5745260 (GRCh38)
- Gene constraint
- LOEUF 1.134 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.49
Similar variants
- EVC p.Ser286Trp Uncertain significance ★★ ⚠ same residue
- EVC p.Ser286Ter Likely pathogenic ★ same residue
- EVC p.Ser286Leu 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
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-ser286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown