Is EVC2 p.Arg9fs (c.24del) pathogenic?

EVC2 p.Arg9fs (c.24del) is classified Pathogenic in EVC2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-05-13). Very rare (popmax 0.00286%, eas); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC2 p.Arg9fs (c.24del)?

EVC2 p.Arg9fs (c.24del) is associated with Ellis-van Creveld syndrome (ClinVar).

How common is EVC2 p.Arg9fs (c.24del) in the general population?

EVC2 p.Arg9fs (c.24del) is very rare (popmax 0.00286%, eas) (gnomAD).

EVC2 p.Arg9fs

c.24del · rs2151750195 · VCV1164043

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00286%, eas)

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 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP -0.031, phastCons 0.077

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00286% East Asian · 1/34,944 alleles

Filtering AF 0.000427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000811% 12/1,480,140 alleles · very rare exomes 12/1,327,968 · genomes 0/152,172 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0037%	26,994
East Asiangrpmax	0.00286%	34,944
South Asian	0.00257%	38,853
Admixed American	0.00231%	43,316
European (non-Finnish)	0.000623%	160,437

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: EVC2
Protein: p.Arg9fs
Coding: c.24del
MANE Select: NM_147127
dbSNP: rs2151750195
Type: Deletion
Location: chr4:5708490 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.33

Full EVC2 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

EVC2 p.Arg9= Likely benign ★ same residue
EVC2 c.222_228+21del Likely pathogenic ★★ same condition
EVC2 c.3361-2del Pathogenic/Likely pathogenic ★★ same condition
EVC2 c.871-2_894del Pathogenic ★★ same condition
EVC2 p.Ala69fs Pathogenic/Likely pathogenic ★★ same condition
EVC2 p.Arg274fs Pathogenic/Likely pathogenic ★★ same condition
EVC2 p.Arg463fs Pathogenic ★★ same condition
EVC2 p.Gly1136fs 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/evc2-p-arg9fs (accessed [today's date]).

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