Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 11 submitters
gnomAD v4.1
Common
common (popmax 64%, eas) — too common for a highly-penetrant pathogenic allele
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 0.6 | GERP -0.25, phastCons 0.084 |
| Overall | ||
| CADD | 16.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
64%
East Asian · 28,706/44,858 alleles
Filtering AF
63.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 63.1%
Overall
40%
645,446/1,613,814 alleles · common
exomes 582,821/1,461,778 · genomes 62,625/152,036 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 64% | 2 |
| South Asian | 53.8% | 2 |
| African / African-American | 47.4% | 2 |
| Amishnot grpmax-eligible | 43.8% | 2 |
| Remaining individualsnot grpmax-eligible | 40.6% | 2 |
| Finnishnot grpmax-eligible | 39.4% | 3 |
| Middle Eastern | 38.7% | 3 |
| European (non-Finnish) | 38% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 35.5% | 3 |
| Admixed American | 34% | 3 |
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.Asn323=
- Coding
- c.969T>C
- MANE Select
- NM_153717
- dbSNP
- rs4688963
- Type
- single nucleotide variant
- Location
- chr4:5748177 (GRCh38)
- Gene constraint
- LOEUF 1.134 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.49
Similar variants
- 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
- EVC c.2304+2T>C 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-asn323 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown