Is GNB3 p.Asn237Ser (c.710A>G) pathogenic?

GNB3 p.Asn237Ser (c.710A>G) is classified Uncertain significance in GNB3 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-12-19). AlphaMissense: likely benign (0.0487); Ultra-rare (popmax 0.0111%, eas); Associated with Inborn genetic diseases.

What condition is associated with GNB3 p.Asn237Ser (c.710A>G)?

GNB3 p.Asn237Ser (c.710A>G) is associated with Inborn genetic diseases (ClinVar).

How common is GNB3 p.Asn237Ser (c.710A>G) in the general population?

GNB3 p.Asn237Ser (c.710A>G) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about GNB3 p.Asn237Ser (c.710A>G)?

AlphaMissense predicts likely benign (score 0.0487) — an in-silico prediction, not a clinical call.

GNB3 p.Asn237Ser

c.710A>G · rs113437937 · VCV2208486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0487 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0487	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -3.60	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.3	GERP 0.58, phastCons 0.07
Regional constraint	o/e 0.90	unconstrained · MANE · 5,607 bp · p 0.03 · regional, not allelic
Overall
CADD	14.13	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 0.0111% East Asian · 5/44,848 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00155% 25/1,610,274 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,970
Admixed American	0.00167%	59,992
Remaining individualsnot grpmax-eligible	0.0016%	62,438
European (non-Finnish)	0.00136%	73,679
African / African-American	0.00133%	75,006
South Asian	0.0011%	91,068

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: GNB3
Protein: p.Asn237Ser
Coding: c.710A>G
MANE Select: NM_031299 · reported on NM_002075
dbSNP: rs113437937
Type: single nucleotide variant
Location: chr12:6845596 (GRCh38)

Full GNB3 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/gnb3-p-asn237ser (accessed [today's date]).

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