Is EVC2 p.Val1182Ser (c.3544_3545delinsTC) pathogenic?

EVC2 p.Val1182Ser (c.35443545delinsTC) is classified Uncertain significance in EVC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-06). Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC2 p.Val1182Ser (c.3544_3545delinsTC)?

EVC2 p.Val1182Ser (c.3544_3545delinsTC) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

EVC2 p.Val1182Ser

c.3544_3545delinsTC · VCV3763835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

acrofacial dysostosis, Weyers type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.4	GERP -4
Regional constraint	o/e 1.14	unconstrained · MANE · 146 kb · p 1.9e-08 · regional, not allelic

Variant & gene context

Gene: EVC2
Protein: p.Val1182Ser
Coding: c.3544_3545delinsTC
MANE Select: NM_147127
Type: Indel
Location: chr4:5568456 (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.Val1182Leu Uncertain significance ★ ⚠ same residue
EVC2 p.Val1182Met Uncertain significance ★ ⚠ same residue
EVC2 p.Val1182= Likely benign ★ same residue
EVC2 p.Ala618fs Likely pathogenic ★ same condition
EVC2 p.Arg952fs Likely pathogenic ★ same condition
EVC2 p.Cys30_Leu31delinsTer Pathogenic ★ same condition
EVC2 p.Gln625fs Likely pathogenic ★ same condition
EVC2 p.Gly251fs 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-val1182ser (accessed [today's date]).

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