Is GNB3 p.Trp211Ter (c.632G>A) pathogenic?

GNB3 p.Trp211Ter (c.632G>A) is classified Conflicting classifications of pathogenicity in GNB3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-06). Ultra-rare (popmax 0.0165%, sas); Associated with GNB3-related disorders.

What condition is associated with GNB3 p.Trp211Ter (c.632G>A)?

GNB3 p.Trp211Ter (c.632G>A) is associated with GNB3-related disorders (ClinVar).

How common is GNB3 p.Trp211Ter (c.632G>A) in the general population?

GNB3 p.Trp211Ter (c.632G>A) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

GNB3 p.Trp211Ter

c.632G>A · rs781795582 · VCV958241

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Conditions

GNB3-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 10
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/91,058 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00105% 17/1,613,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,071
European (non-Finnish)	0.000169%	589,998

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.Trp211Ter
Coding: c.632G>A
MANE Select: NM_002075
dbSNP: rs781795582
Type: single nucleotide variant
Location: chr12:6843911 (GRCh38)
Gene constraint: LOEUF 1.072 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.19 · 2 PDB

Full GNB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GNB3-related disorders

Similar variants

GNB3 c.57+2T>C Likely pathogenic ★ same condition
GNB3 p.Cys121Ter Likely pathogenic ★ same condition
GNB3 c.430+1G>A Conflicting classifications of pathogenicity ★ same condition
GNB3 c.96+2T>G Conflicting classifications of pathogenicity ★ same condition
GNB3 p.Glu38fs Likely pathogenic ★ same condition
GNB3 p.Val39fs Likely pathogenic ★ same condition
GNB3 p.Asn237fs Conflicting classifications of pathogenicity ★ same condition
GNB3 c.203+6G>A Uncertain significance ★★ same type

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-trp211ter (accessed [today's date]).

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