EVC2 p.Arg687=
c.2061T>C · rs73198153 · VCV262609
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Common
common (popmax 24.7%, afr) — 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 -1.9 | GERP -3.8 |
| Overall | ||
| CADD | 1.268 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
24.7%
African / African-American · 18,544/74,956 alleles
Filtering AF
24.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 24.3%
Overall
6.53%
105,418/1,613,516 alleles · common
exomes 88,808/1,461,378 · genomes 16,610/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 24.7% | 4 |
| South Asian | 11.2% | 9 |
| Amishnot grpmax-eligible | 8.33% | 12 |
| Middle Eastern | 7.32% | 14 |
| Remaining individualsnot grpmax-eligible | 6.72% | 15 |
| European (non-Finnish) | 5.49% | 18 |
| Admixed American | 4.76% | 21 |
| Ashkenazi Jewishnot grpmax-eligible | 4.52% | 22 |
| Finnishnot grpmax-eligible | 4.37% | 23 |
| East Asian | 0.332% | 301 |
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.Arg687=
- Coding
- c.2061T>C
- MANE Select
- NM_147127
- dbSNP
- rs73198153
- Type
- single nucleotide variant
- Location
- chr4:5622977 (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.Arg687Cys Uncertain significance ★★ ⚠ same residue
- EVC2 p.Arg687His 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
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-arg687 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown