Is EVC2 p.Ala975Val (c.2924C>T) pathogenic?

EVC2 p.Ala975Val (c.2924C>T) is classified Uncertain significance in EVC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely benign (0.1072); Ultra-rare (popmax 0.0439%, sas); Associated with Inborn genetic diseases.

What condition is associated with EVC2 p.Ala975Val (c.2924C>T)?

EVC2 p.Ala975Val (c.2924C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EVC2 p.Ala975Val (c.2924C>T) in the general population?

EVC2 p.Ala975Val (c.2924C>T) is ultra-rare (popmax 0.0439%, sas) (gnomAD).

What do computational predictors say about EVC2 p.Ala975Val (c.2924C>T)?

AlphaMissense predicts likely benign (score 0.1072) — an in-silico prediction, not a clinical call.

EVC2 p.Ala975Val

c.2924C>T · rs573195320 · VCV2226340

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1072 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0439%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1072	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -6.26	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 -0.014	GERP -3.2
Regional constraint	o/e 1.14	unconstrained · MANE · 146 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	11.92	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 0.0439% South Asian · 40/91,074 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00335% 54/1,614,018 alleles · ultra-rare exomes 52/1,461,892 · genomes 2/152,126 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0439%	2,277
Admixed American	0.00333%	30,001
African / African-American	0.00267%	37,458
East Asian	0.00223%	44,872
Finnishnot grpmax-eligible	0.00156%	64,028
European (non-Finnish)	0.000678%	147,505

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.Ala975Val
Coding: c.2924C>T
MANE Select: NM_147127
dbSNP: rs573195320
Type: single nucleotide variant
Location: chr4:5584756 (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

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

Similar variants

EVC2 p.Ala975= Likely benign ★★ same residue
EVC2 p.Ala975Ser Uncertain significance ★ ⚠ same residue
EVC2 p.Gln1089Ter Pathogenic ★★ same condition
EVC2 p.Ala1132Val Uncertain significance ★★ ⚠ same condition
EVC2 p.Ala1150Asp Uncertain significance ★★ ⚠ same condition
EVC2 p.Ala1260Val Uncertain significance ★★ ⚠ same condition
EVC2 p.Ala618Thr Uncertain significance ★★ ⚠ same condition
EVC2 p.Ala703Val Uncertain significance ★★ ⚠ 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-ala975val (accessed [today's date]).

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