Is EVC p.Arg632Pro (c.1895G>C) pathogenic?

EVC p.Arg632Pro (c.1895G>C) is classified Uncertain significance in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-09). AlphaMissense: ambiguous (0.3626); Very rare (popmax 0.000424%, nfe); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Arg632Pro (c.1895G>C)?

EVC p.Arg632Pro (c.1895G>C) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Arg632Pro (c.1895G>C) in the general population?

EVC p.Arg632Pro (c.1895G>C) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about EVC p.Arg632Pro (c.1895G>C)?

AlphaMissense predicts ambiguous (score 0.3626) — an in-silico prediction, not a clinical call.

EVC p.Arg632Pro

c.1895G>C · rs535632933 · VCV1464567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3626 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Ellis-van Creveld syndrome

Computational evidence

Protein change
AlphaMissense	0.3626	ambiguous
REVEL	0.178	moderately benign-leaning
SaProt	LLR -12.76	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.6	GERP -3.6
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	15.35	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,548 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,612,660 alleles · very rare exomes 5/1,460,430 · genomes 0/152,230 · joint denominator

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.Arg632Pro
Coding: c.1895G>C
MANE Select: NM_153717
dbSNP: rs535632933
Type: single nucleotide variant
Location: chr4:5797030 (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.Arg632Gln Uncertain significance ★ ⚠ same residue
EVC p.Arg632Trp Uncertain significance ★ ⚠ same residue
EVC p.Arg632= 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

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-arg632pro (accessed [today's date]).

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