Is EVC p.Ala29Pro (c.85G>C) pathogenic?

EVC p.Ala29Pro (c.85G>C) is classified Uncertain significance in EVC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-02-06). AlphaMissense: likely benign (0.2087); No allele count reported in gnomAD v4.1 (AN 1,057,440); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Ala29Pro (c.85G>C)?

EVC p.Ala29Pro (c.85G>C) is associated with Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Ala29Pro (c.85G>C) in the general population?

EVC p.Ala29Pro (c.85G>C) is no allele count reported in gnomAD v4.1 (AN 1,057,440) (gnomAD).

What do computational predictors say about EVC p.Ala29Pro (c.85G>C)?

AlphaMissense predicts likely benign (score 0.2087) — an in-silico prediction, not a clinical call.

EVC p.Ala29Pro

c.85G>C · VCV4067553

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2087 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,057,440)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ellis-van Creveld syndrome

Computational evidence

Protein change
AlphaMissense	0.2087	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -6.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 0.16, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	20.8	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

No allele count reported in gnomAD v4.1 (AN 1,057,440). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EVC
Protein: p.Ala29Pro
Coding: c.85G>C
MANE Select: NM_153717
Type: single nucleotide variant
Location: chr4:5711465 (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

Similar variants

EVC p.Ala29Val Conflicting classifications of pathogenicity ★ ⚠ same residue
EVC p.Ala29= 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

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-ala29pro (accessed [today's date]).

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