EVC p.Arg718=
c.2154G>A · rs1714415040 · VCV1563762
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000427%, 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 1.8 | GERP 0.7, phastCons 1 |
| Overall | ||
| CADD | 3.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000427%
European (non-Finnish) · 5/1,171,562 alleles
Filtering AF
0.000125%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.1e-05%
Overall
0.000314%
5/1,593,002 alleles · very rare
exomes 5/1,440,632 · genomes 0/152,370 · 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
- EVC
- Protein
- p.Arg718=
- Coding
- c.2154G>A
- MANE Select
- NM_153717
- dbSNP
- rs1714415040
- Type
- single nucleotide variant
- Location
- chr4:5798642 (GRCh38)
- Gene constraint
- LOEUF 1.134 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.49
Similar variants
- EVC p.Arg718Trp Uncertain significance ★★ ⚠ same residue
- EVC p.Arg718Gly Uncertain significance ★ ⚠ 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
- EVC c.1886+5G>A 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-arg718 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown