EVC2 p.His717=
c.2151C>T · rs144584049 · VCV194441
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 10 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.56%, mid)
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 -0.038 | GERP -3.8 |
| Overall | ||
| CADD | 1.676 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.56%
Middle Eastern · 155/6,062 alleles
Filtering AF
2.23%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.1%
Overall
0.242%
3,907/1,614,170 alleles · low-frequency
exomes 3,553/1,461,868 · genomes 354/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 2.56% | 39 |
| Ashkenazi Jewishnot grpmax-eligible | 1.23% | 81 |
| Admixed American | 0.5% | 200 |
| Remaining individualsnot grpmax-eligible | 0.461% | 217 |
| South Asian | 0.358% | 279 |
| European (non-Finnish) | 0.202% | 494 |
| African / African-American | 0.112% | 894 |
| East Asian | 0.00223% | 44,872 |
| Finnishnot grpmax-eligible | 0.00156% | 64,008 |
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.His717=
- Coding
- c.2151C>T
- MANE Select
- NM_147127
- dbSNP
- rs144584049
- Type
- single nucleotide variant
- Location
- chr4:5622887 (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.His717fs Pathogenic ★ 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-his717 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown