Is EVC p.Arg340= (c.1020A>G) pathogenic?

EVC p.Arg340= (c.1020A>G) is classified Likely benign in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-13). Absent from gnomAD v4.1; Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Arg340= (c.1020A>G)?

EVC p.Arg340= (c.1020A>G) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Arg340= (c.1020A>G) in the general population?

EVC p.Arg340= (c.1020A>G) is absent from gnomAD v4.1 (gnomAD).

EVC p.Arg340=

c.1020A>G · rs2475162874 · VCV2030164

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.078	GERP -3.9, phastCons 0.4
Overall
CADD	7.977	PHRED · no single calibrated threshold — expert panels disagree

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.Arg340=
Coding: c.1020A>G
MANE Select: NM_153717
dbSNP: rs2475162874
Type: single nucleotide variant
Location: chr4:5748228 (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.Arg340Ter Pathogenic/Likely pathogenic ★★ same residue
EVC p.Arg340Gln Uncertain significance ★★ ⚠ same residue
EVC p.Arg340Pro 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-arg340 (accessed [today's date]).

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