Is EVC p.Pro152= (c.456G>A) pathogenic?

EVC p.Pro152= (c.456G>A) is classified Likely benign in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). Very rare (popmax 0.00333%, amr); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Pro152= (c.456G>A)?

EVC p.Pro152= (c.456G>A) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Pro152= (c.456G>A) in the general population?

EVC p.Pro152= (c.456G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

EVC p.Pro152=

c.456G>A · rs776773987 · VCV1122054

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Ellis-van Creveld syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.30	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -7.8	GERP -3.4
Overall
CADD	6.399	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,990 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00242% 39/1,613,966 alleles · very rare exomes 37/1,461,888 · genomes 2/152,078 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,995
European (non-Finnish)	0.00288%	34,706
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00134%	74,894
South Asian	0.0011%	91,070

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.Pro152=
Coding: c.456G>A
MANE Select: NM_153717
dbSNP: rs776773987
Type: single nucleotide variant
Location: chr4:5731496 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49
Residue 152: 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

Also linked: acrofacial dysostosis, Weyers type

Similar variants

EVC p.Pro152Leu Uncertain significance ★★ ⚠ same residue
EVC p.Pro152Ala Uncertain significance ★ ⚠ same residue
EVC c.1098+1G>A Pathogenic/Likely pathogenic ★★ same condition
EVC c.175-2A>G Pathogenic/Likely pathogenic ★★ same condition
EVC c.1777-1G>A Pathogenic/Likely pathogenic ★★ same condition
EVC c.1777-2A>G Pathogenic/Likely pathogenic ★★ same condition
EVC c.1886+1G>C Likely pathogenic ★★ same condition
EVC c.1886+5G>A 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-pro152 (accessed [today's date]).

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