Is EVC p.Ala976Val (c.2927C>T) pathogenic?

EVC p.Ala976Val (c.2927C>T) is classified Uncertain significance in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-19). AlphaMissense: likely benign (0.0789); Absent from gnomAD v4.1; Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Ala976Val (c.2927C>T)?

EVC p.Ala976Val (c.2927C>T) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Ala976Val (c.2927C>T) in the general population?

EVC p.Ala976Val (c.2927C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EVC p.Ala976Val (c.2927C>T)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

EVC p.Ala976Val

c.2927C>T · rs1716832971 · VCV2048338

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ellis-van Creveld syndrome

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -2.9
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	4.642	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EVC
Protein: p.Ala976Val
Coding: c.2927C>T
MANE Select: NM_153717
dbSNP: rs1716832971
Type: single nucleotide variant
Location: chr4:5810985 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49
Residue 976: the 'disordered' region

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.Ala976= Likely benign ★ 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-ala976val (accessed [today's date]).

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