EVC2 p.Arg677=
c.2029C>A · rs73198165 · VCV235459
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 9 submitters
gnomAD v4.1
Rare
rare (popmax 0.75%, 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 5.4 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 7.928 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.75%
European (non-Finnish) · 8,846/1,179,992 alleles
Filtering AF
0.737%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.731%
Overall
0.601%
9,701/1,614,028 alleles · rare
exomes 9,149/1,461,812 · genomes 552/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.75% | 133 |
| Remaining individualsnot grpmax-eligible | 0.552% | 181 |
| Admixed American | 0.26% | 385 |
| South Asian | 0.188% | 533 |
| Middle Eastern | 0.148% | 674 |
| African / African-American | 0.117% | 853 |
| Finnishnot grpmax-eligible | 0.0969% | 1,032 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0574% | 1,742 |
| East Asian | 0.0156% | 6,409 |
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.Arg677=
- Coding
- c.2029C>A
- MANE Select
- NM_147127
- dbSNP
- rs73198165
- Type
- single nucleotide variant
- Location
- chr4:5625766 (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.Arg677Ter Pathogenic ★★ same residue
- EVC2 p.Arg677Pro 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-arg677 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown