Is EVC p.Arg194= (c.582G>A) pathogenic?

EVC p.Arg194= (c.582G>A) is classified Likely benign in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). Very rare (popmax 0.00364%, nfe); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Arg194= (c.582G>A)?

EVC p.Arg194= (c.582G>A) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Arg194= (c.582G>A) in the general population?

EVC p.Arg194= (c.582G>A) is very rare (popmax 0.00364%, nfe) (gnomAD).

EVC p.Arg194=

c.582G>A · rs200101865 · VCV1498334

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Conditions

Ellis-van Creveld syndrome

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 -0.38	GERP -3.4
Overall
CADD	5.894	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00364% European (non-Finnish) · 43/1,180,030 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00285% 46/1,614,006 alleles · very rare exomes 45/1,461,880 · genomes 1/152,126 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,443
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-American	0.00134%	74,906

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.Arg194=
Coding: c.582G>A
MANE Select: NM_153717
dbSNP: rs200101865
Type: single nucleotide variant
Location: chr4:5731622 (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.Arg194Trp Uncertain significance ★★ ⚠ same residue
EVC p.Arg194Gln Uncertain significance ★ ⚠ same residue
EVC p.Arg194Pro Uncertain significance ★ ⚠ same residue
EVC p.Arg194_Val195insTer Pathogenic ★ 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

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-arg194 (accessed [today's date]).

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