Is EVC2 p.Arg1141= (c.3423G>A) pathogenic?

EVC2 p.Arg1141= (c.3423G>A) is classified Likely benign in EVC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). No allele count reported in gnomAD v4.1 (AN 1,607,554); Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC2 p.Arg1141= (c.3423G>A)?

EVC2 p.Arg1141= (c.3423G>A) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC2 p.Arg1141= (c.3423G>A) in the general population?

EVC2 p.Arg1141= (c.3423G>A) is no allele count reported in gnomAD v4.1 (AN 1,607,554) (gnomAD).

EVC2 p.Arg1141=

c.3423G>A · rs1577099807 · VCV765330

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,554)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.53	GERP -2.6, phastCons 0.042
Overall
CADD	4.053	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,607,554). 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: EVC2
Protein: p.Arg1141=
Coding: c.3423G>A
MANE Select: NM_147127
dbSNP: rs1577099807
Type: single nucleotide variant
Location: chr4:5568578 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.33

Full EVC2 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

EVC2 p.Arg1141Gln Uncertain significance ★★ ⚠ same residue
EVC2 p.Arg1141Trp Uncertain significance ★★ ⚠ same residue
EVC2 c.2046+1G>A Likely pathogenic ★★ same condition
EVC2 c.2047-2A>G Likely pathogenic ★★ same condition
EVC2 c.229-1G>T Likely pathogenic ★★ same condition
EVC2 c.229-2A>G Likely pathogenic ★★ same condition
EVC2 c.3360+1G>A Pathogenic ★★ same condition
EVC2 c.3659+2T>C 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/evc2-p-arg1141 (accessed [today's date]).

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