Is EVC2 p.Met784Val (c.2350A>G) pathogenic?

EVC2 p.Met784Val (c.2350A>G) is classified Conflicting classifications of pathogenicity in EVC2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1031); Rare (popmax 0.345%, mid); Associated with Inborn genetic diseases.

What condition is associated with EVC2 p.Met784Val (c.2350A>G)?

EVC2 p.Met784Val (c.2350A>G) is associated with Inborn genetic diseases, acrofacial dysostosis, Weyers type, Ellis-van Creveld syndrome (ClinVar).

How common is EVC2 p.Met784Val (c.2350A>G) in the general population?

EVC2 p.Met784Val (c.2350A>G) is rare (popmax 0.345%, mid) (gnomAD).

What do computational predictors say about EVC2 p.Met784Val (c.2350A>G)?

AlphaMissense predicts likely benign (score 0.1031) — an in-silico prediction, not a clinical call.

EVC2 p.Met784Val

c.2350A>G · rs202191109 · VCV546567

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1031 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.345%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1031	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -7.00	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 -1	GERP -4.1
Regional constraint	o/e 1.14	unconstrained · MANE · 146 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	1.196	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.345% Middle Eastern · 21/6,082 alleles

Filtering AF 0.231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.194%

Overall 0.0062% 100/1,613,904 alleles · rare exomes 96/1,461,878 · genomes 4/152,026 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.345%	290
South Asian	0.0362%	2,760
Remaining individualsnot grpmax-eligible	0.0192%	5,207
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
Admixed American	0.00333%	29,995
European (non-Finnish)	0.00254%	39,334

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.Met784Val
Coding: c.2350A>G
MANE Select: NM_147127
dbSNP: rs202191109
Type: single nucleotide variant
Location: chr4:5622688 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.33
Residue 784: the 'disordered' region

Full EVC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: acrofacial dysostosis, Weyers type Ellis-van Creveld syndrome

Similar variants

EVC2 c.2046+1G>A Likely pathogenic ★★ same condition
EVC2 c.2047-2A>G Likely pathogenic ★★ same condition
EVC2 c.229-1G>T Likely pathogenic ★★ same condition
EVC2 c.229-2A>G Likely pathogenic ★★ same condition
EVC2 c.3360+1G>A Pathogenic ★★ same condition
EVC2 c.3659+2T>C Pathogenic/Likely pathogenic ★★ same condition
EVC2 c.450+2T>C Likely pathogenic ★★ same condition
EVC2 c.451-2A>G 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/evc2-p-met784val (accessed [today's date]).

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