EVC2 p.Arg61=
c.183G>A · rs2474142040 · VCV2027535
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000179%, nfe)
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 -0.088 | GERP -0.014 |
| Overall | ||
| CADD | 5.499 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000179%
European (non-Finnish) · 2/1,117,192 alleles
Filtering AF
3e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000136%
2/1,471,088 alleles · very rare
exomes 2/1,319,106 · genomes 0/151,982 · joint denominator
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.Arg61=
- Coding
- c.183G>A
- MANE Select
- NM_147127
- dbSNP
- rs2474142040
- Type
- single nucleotide variant
- Location
- chr4:5708331 (GRCh38)
- Gene constraint
- LOEUF 1.092 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 73.33
- Residue 61
- the 'disordered' region
Similar variants
- 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
- EVC2 c.451-2A>G 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-arg61 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown