Is EVC p.Ala774= (c.2322G>C) pathogenic?

EVC p.Ala774= (c.2322G>C) is classified Conflicting classifications of pathogenicity in EVC (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-02-06). Rare (popmax 0.202%, sas); Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC p.Ala774= (c.2322G>C)?

EVC p.Ala774= (c.2322G>C) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Ala774= (c.2322G>C) in the general population?

EVC p.Ala774= (c.2322G>C) is rare (popmax 0.202%, sas) (gnomAD).

EVC p.Ala774=

c.2322G>C · rs150373930 · VCV194682

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.202%, sas)

Conditions

acrofacial dysostosis, Weyers type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.3	GERP -3.2
Overall
CADD	0.223	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.202% South Asian · 184/91,046 alleles

Filtering AF 0.178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.169%

Overall 0.0891% 1,437/1,613,674 alleles · rare exomes 1,358/1,461,358 · genomes 79/152,316 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.202%	495
Middle Eastern	0.105%	949
European (non-Finnish)	0.101%	992
Remaining individualsnot grpmax-eligible	0.0608%	1,644
African / African-American	0.02%	5,003
Admixed American	0.00833%	12,004

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.Ala774=
Coding: c.2322G>C
MANE Select: NM_153717
dbSNP: rs150373930
Type: single nucleotide variant
Location: chr4:5801967 (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

acrofacial dysostosis, Weyers type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ellis-van Creveld syndrome

Similar variants

EVC p.Ala774Val 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
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-ala774 (accessed [today's date]).

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