Is EVC p.Leu257= (c.771A>G) pathogenic?

EVC p.Leu257= (c.771A>G) is classified Benign in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-25). Very rare (popmax 0.00135%, afr); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Leu257= (c.771A>G)?

EVC p.Leu257= (c.771A>G) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Leu257= (c.771A>G) in the general population?

EVC p.Leu257= (c.771A>G) is very rare (popmax 0.00135%, afr) (gnomAD).

EVC p.Leu257=

c.771A>G · rs756340487 · VCV1551684

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Conditions

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 -0.074	GERP -3.4, phastCons 0.022
Overall
CADD	5.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00135% African / African-American · 1/73,836 alleles

Overall 0.000129% 2/1,544,990 alleles · very rare exomes 2/1,392,662 · genomes 0/152,328 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00135%	73,836
European (non-Finnish)	8.94e-05%	1,118,616

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.Leu257=
Coding: c.771A>G
MANE Select: NM_153717
dbSNP: rs756340487
Type: single nucleotide variant
Location: chr4:5741784 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49

Full EVC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Ellis-van Creveld syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acrofacial dysostosis, Weyers type

Similar variants

EVC p.Leu257Gln Likely pathogenic ★ ⚠ 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
EVC c.1886+5G>T 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/evc-p-leu257 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown