Is EVC p.Val790Met (c.2368G>A) pathogenic?

EVC p.Val790Met (c.2368G>A) is classified Uncertain significance in EVC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-24). AlphaMissense: likely benign (0.1937); Ultra-rare (popmax 0.0165%, mid); Associated with Ellis-van Creveld syndrome.

What condition is associated with EVC p.Val790Met (c.2368G>A)?

EVC p.Val790Met (c.2368G>A) is associated with Ellis-van Creveld syndrome, acrofacial dysostosis, Weyers type (ClinVar).

How common is EVC p.Val790Met (c.2368G>A) in the general population?

EVC p.Val790Met (c.2368G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about EVC p.Val790Met (c.2368G>A)?

AlphaMissense predicts likely benign (score 0.1937) — an in-silico prediction, not a clinical call.

EVC p.Val790Met

c.2368G>A · rs749975914 · VCV2193548

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1937 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ellis-van Creveld syndrome

Computational evidence

Protein change
AlphaMissense	0.1937	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -7.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.8	GERP 1.6, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 100 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,068 alleles

Filtering AF 0.00921% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.000991% 16/1,614,080 alleles · ultra-rare exomes 9/1,461,846 · genomes 7/152,234 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,068
African / African-American	0.016%	6,245
Remaining individualsnot grpmax-eligible	0.0032%	31,239
European (non-Finnish)	8.47e-05%	1,180,036

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.Val790Met
Coding: c.2368G>A
MANE Select: NM_153717
dbSNP: rs749975914
Type: single nucleotide variant
Location: chr4:5802013 (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.Val790= Likely benign ★ 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
EVC c.1886+5G>T 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-val790met (accessed [today's date]).

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