Is EVC p.Val948= (c.2844G>T) pathogenic?

EVC p.Val948= (c.2844G>T) is classified Likely benign in EVC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-08). Very rare (popmax 0.00267%, afr); Associated with acrofacial dysostosis, Weyers type.

What condition is associated with EVC p.Val948= (c.2844G>T)?

EVC p.Val948= (c.2844G>T) is associated with acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC p.Val948= (c.2844G>T) in the general population?

EVC p.Val948= (c.2844G>T) is very rare (popmax 0.00267%, afr) (gnomAD).

EVC p.Val948=

c.2844G>T · rs2474706441 · VCV2931859

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

acrofacial dysostosis, Weyers type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7	GERP -3.1
Overall
CADD	0.008	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,028 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,794 alleles · very rare exomes 2/1,461,542 · genomes 0/152,252 · 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.Val948=
Coding: c.2844G>T
MANE Select: NM_153717
dbSNP: rs2474706441
Type: single nucleotide variant
Location: chr4:5810400 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49
Residue 948: the 'disordered' region

Full EVC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

acrofacial dysostosis, Weyers type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Ellis-van Creveld syndrome

Similar variants

EVC p.Val948Met Uncertain significance ★ ⚠ same residue
EVC p.Val948fs 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-val948 (accessed [today's date]).

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