Is EVC p.Leu161fs (c.482del) pathogenic?

EVC p.Leu161fs (c.482del) is classified Likely pathogenic in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-28). Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Leu161fs (c.482del)?

EVC p.Leu161fs (c.482del) is associated with Ellis-van Creveld syndrome (ClinVar).

EVC p.Leu161fs

c.482del · VCV4816941

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Ellis-van Creveld syndrome

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 4 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP 0.65, phastCons 1

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

Variant & gene context

Gene: EVC
Protein: p.Leu161fs
Coding: c.482del
MANE Select: NM_153717
Type: Deletion
Location: chr4:5731522 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49
Residue 161: the 'disordered' region

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

Similar variants

EVC c.1783_1886+40del Pathogenic ★★ same condition
EVC c.1887-5_1904del Pathogenic/Likely pathogenic ★★ same condition
EVC c.2782+1del Pathogenic ★★ same condition
EVC p.Ala565fs Pathogenic ★★ same condition
EVC p.Asn68fs Pathogenic ★★ same condition
EVC p.Asp132fs Pathogenic/Likely pathogenic ★★ same condition
EVC p.Gln424fs Pathogenic/Likely pathogenic ★★ same condition
EVC p.Gln584fs 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-leu161fs (accessed [today's date]).

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