Is GNB2 p.Arg129His (c.386G>A) pathogenic?

GNB2 p.Arg129His (c.386G>A) is classified Uncertain significance in GNB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely pathogenic (0.8147); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with GNB2 p.Arg129His (c.386G>A)?

GNB2 p.Arg129His (c.386G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GNB2 p.Arg129His (c.386G>A) in the general population?

GNB2 p.Arg129His (c.386G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about GNB2 p.Arg129His (c.386G>A)?

AlphaMissense predicts likely pathogenic (score 0.8147) — an in-silico prediction, not a clinical call.

GNB2 p.Arg129His

c.386G>A · rs1201205764 · VCV3100600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8147 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8147	likely pathogenic
REVEL	0.309	indeterminate
SaProt	LLR -11.23	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 5, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 2,532 bp · p 8.1e-18 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00267% African / African-American · 2/74,934 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000372% 6/1,613,298 alleles · very rare exomes 5/1,461,072 · genomes 1/152,226 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,467
European (non-Finnish)	0.000339%	295,003

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.Arg129His
Coding: c.386G>A
MANE Select: NM_005273
dbSNP: rs1201205764
Type: single nucleotide variant
Location: chr7:100677616 (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.Arg129= Likely benign ★★ same residue
GNB2 p.Arg129Cys Uncertain significance ★ ⚠ same residue
GNB2 p.Arg129Ser Uncertain significance ★ ⚠ same residue
GNB2 p.Thr198Lys Uncertain significance ★★ ⚠ 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.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-arg129his (accessed [today's date]).

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