Is EVC p.Arg632= (c.1896G>C) pathogenic?

EVC p.Arg632= (c.1896G>C) is classified Likely benign in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-19). Very rare (popmax 0.000254%, nfe); Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC p.Arg632= (c.1896G>C)?

EVC p.Arg632= (c.1896G>C) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Arg632= (c.1896G>C) in the general population?

EVC p.Arg632= (c.1896G>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

EVC p.Arg632=

c.1896G>C · rs758327867 · VCV1148772

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

acrofacial dysostosis, Weyers type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.9	GERP 0.74, phastCons 0.005
Overall
CADD	8.684	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,648 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,612,816 alleles · very rare exomes 3/1,460,522 · genomes 0/152,294 · 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.Arg632=
Coding: c.1896G>C
MANE Select: NM_153717
dbSNP: rs758327867
Type: single nucleotide variant
Location: chr4:5797031 (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.Arg632Gln Uncertain significance ★ ⚠ same residue
EVC p.Arg632Pro Uncertain significance ★ ⚠ same residue
EVC p.Arg632Trp 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

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-arg632 (accessed [today's date]).

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