Is GNB2 p.Val90Ile (c.268G>A) pathogenic?

GNB2 p.Val90Ile (c.268G>A) is classified Uncertain significance in GNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-22). AlphaMissense: likely benign (0.089); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with GNB2 p.Val90Ile (c.268G>A)?

GNB2 p.Val90Ile (c.268G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GNB2 p.Val90Ile (c.268G>A) in the general population?

GNB2 p.Val90Ile (c.268G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about GNB2 p.Val90Ile (c.268G>A)?

AlphaMissense predicts likely benign (score 0.089) — an in-silico prediction, not a clinical call.

GNB2 p.Val90Ile

c.268G>A · rs199810512 · VCV2381585

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.089 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.089	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -11.80	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 3.8, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 2,532 bp · p 8.1e-18 · regional, not allelic
Overall
CADD	20.7	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 0.00167% Admixed American · 1/60,006 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00124% 20/1,613,290 alleles · very rare exomes 17/1,461,046 · genomes 3/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,468
European (non-Finnish)	0.00153%	65,552

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: GNB2
Protein: p.Val90Ile
Coding: c.268G>A
MANE Select: NM_005273
dbSNP: rs199810512
Type: single nucleotide variant
Location: chr7:100677498 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 96.89 · 1 PDB

Full GNB2 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

GNB2 p.Thr198Lys Uncertain significance ★★ ⚠ same condition
GNB2 p.Arg129= Likely benign ★★ same condition
GNB2 p.Ala106Thr Uncertain significance ★ ⚠ same condition
GNB2 p.Ala309Thr Uncertain significance ★ ⚠ same condition
GNB2 p.Ala35Val Uncertain significance ★ ⚠ same condition
GNB2 p.Arg129Cys Uncertain significance ★ ⚠ same condition
GNB2 p.Arg129His Uncertain significance ★ ⚠ same condition
GNB2 p.Arg150Cys 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/gnb2-p-val90ile (accessed [today's date]).

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