Is GNB5 p.Val8Ile (c.22G>A) pathogenic?

GNB5 p.Val8Ile (c.22G>A) is classified Benign/Likely benign in GNB5 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1199); Rare (popmax 0.454%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GNB5 p.Val8Ile (c.22G>A)?

GNB5 p.Val8Ile (c.22G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GNB5 p.Val8Ile (c.22G>A) in the general population?

GNB5 p.Val8Ile (c.22G>A) is rare (popmax 0.454%, nfe) (gnomAD).

What do computational predictors say about GNB5 p.Val8Ile (c.22G>A)?

AlphaMissense predicts likely benign (score 0.1199) — an in-silico prediction, not a clinical call.

GNB5 p.Val8Ile

c.22G>A · rs41277710 · VCV770786

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1199 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.454%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1199	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.9	GERP 0.92, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 62 kb · p 0.083 · regional, not allelic
Overall
CADD	22.7	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 0.454% European (non-Finnish) · 5,352/1,179,546 alleles

Filtering AF 0.444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.439%

Overall 0.364% 5,872/1,613,402 alleles · rare exomes 5,509/1,461,312 · genomes 363/152,090 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.454%	220
Remaining individualsnot grpmax-eligible	0.323%	309
Admixed American	0.178%	561
Finnishnot grpmax-eligible	0.142%	703
African / African-American	0.136%	735
Middle Eastern	0.033%	3,030
South Asian	0.0165%	6,070
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592

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: GNB5
Protein: p.Val8Ile
Coding: c.22G>A
MANE Select: NM_016194
dbSNP: rs41277710
Type: single nucleotide variant
Location: chr15:52184655 (GRCh38)

Full GNB5 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

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/gnb5-p-val8ile (accessed [today's date]).

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