Is EVC p.Arg13fs (c.37_38del) pathogenic?

EVC p.Arg13fs (c.3738del) is classified Pathogenic in EVC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-26). Very rare (popmax 0.000117%, nfe); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Arg13fs (c.37_38del)?

EVC p.Arg13fs (c.37_38del) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Arg13fs (c.37_38del) in the general population?

EVC p.Arg13fs (c.37_38del) is very rare (popmax 0.000117%, nfe) (gnomAD).

EVC p.Arg13fs

c.37_38del · rs1722986802 · VCV1013604

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000117%, 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 1 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP 0.19, phastCons 0.98

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000117% European (non-Finnish) · 1/857,854 alleles

Overall 9.77e-05% 1/1,023,234 alleles · very rare exomes 1/875,944 · genomes 0/147,290 · 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.Arg13fs
Coding: c.37_38del
MANE Select: NM_153717
dbSNP: rs1722986802
Type: Microsatellite
Location: chr4:5711413 (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.Arg13= Likely benign ★ same residue
EVC p.Arg13Trp Likely benign ★ same residue
EVC p.Cys554_Asp555delinsTer Pathogenic/Likely pathogenic ★★ same condition
EVC p.Leu346fs Pathogenic ★★ same condition
EVC p.Lys302del Pathogenic/Likely pathogenic ★★ same condition
EVC p.Phe583fs Pathogenic/Likely pathogenic ★★ same condition
EVC p.39GL[4] Uncertain significance ★★ same condition
EVC c.2895-10_2895-9del Benign/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-arg13fs (accessed [today's date]).

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