Is EVC p.Thr75fs (c.222dup) pathogenic?

EVC p.Thr75fs (c.222dup) is classified Likely pathogenic in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Thr75fs (c.222dup)?

EVC p.Thr75fs (c.222dup) is associated with Ellis-van Creveld syndrome (ClinVar).

EVC p.Thr75fs

c.222dup · VCV4816930

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 2 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2	GERP -0.74, phastCons 1

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

Variant & gene context

Gene: EVC
Protein: p.Thr75fs
Coding: c.222dup
MANE Select: NM_153717
Type: Duplication
Location: chr4:5719294 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49
Residue 75: 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 p.Thr75= Likely benign ★ same residue
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

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-thr75fs (accessed [today's date]).

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