Is EVC p.Ala489fs (c.1452_1464dup) pathogenic?

EVC p.Ala489fs (c.14521464dup) is classified Pathogenic in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC p.Ala489fs (c.1452_1464dup)?

EVC p.Ala489fs (c.1452_1464dup) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

EVC p.Ala489fs

c.1452_1464dup · VCV3755812

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP -0.64, phastCons 0.007

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: EVC
Protein: p.Ala489fs
Coding: c.1452_1464dup
MANE Select: NM_153717
Type: Duplication
Location: chr4:5753920 (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.Arg304fs Pathogenic/Likely pathogenic ★★ same condition
EVC p.Glu292Ter Pathogenic ★★ same condition
EVC p.Glu552fs Pathogenic/Likely pathogenic ★★ same condition
EVC p.His233fs Pathogenic/Likely pathogenic ★★ same condition
EVC p.Lys252fs Pathogenic ★★ same condition
EVC p.Thr463fs Pathogenic/Likely pathogenic ★★ same condition
EVC p.Tyr258Ter Pathogenic/Likely pathogenic ★★ same condition
EVC c.2782+13dup Likely benign ★★ 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-ala489fs (accessed [today's date]).

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