Is EVC p.Leu262fs (c.784del) pathogenic?

EVC p.Leu262fs (c.784del) is classified Pathogenic in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-10). Very rare (popmax 9.16e-05%, nfe); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Leu262fs (c.784del)?

EVC p.Leu262fs (c.784del) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Leu262fs (c.784del) in the general population?

EVC p.Leu262fs (c.784del) is very rare (popmax 9.16e-05%, nfe) (gnomAD).

EVC p.Leu262fs

c.784del · rs1560315890 · VCV1453102

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 9.16e-05%, nfe)

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 6 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.16e-05% European (non-Finnish) · 1/1,091,720 alleles

Overall 6.6e-05% 1/1,515,184 alleles · very rare exomes 1/1,362,904 · genomes 0/152,280 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EVC
Protein: p.Leu262fs
Coding: c.784del
MANE Select: NM_153717
dbSNP: rs1560315890
Type: Deletion
Location: chr4:5741796 (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

Ellis-van Creveld syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acrofacial dysostosis, Weyers type

Similar variants

EVC p.Leu262= Likely benign ★ same residue
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

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-leu262fs (accessed [today's date]).

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