Is GNB3 p.Ser201= (c.603G>A) pathogenic?

GNB3 p.Ser201= (c.603G>A) is classified Uncertain significance in GNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). Very rare (popmax 0.00223%, eas).

How common is GNB3 p.Ser201= (c.603G>A) in the general population?

GNB3 p.Ser201= (c.603G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

GNB3 p.Ser201=

c.603G>A · rs782790179 · VCV1908007

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ1.00	acceptor gain · deltas
Pangolin	Δ0.89	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.15	GERP -5, phastCons 0.13
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,874 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,613,766 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
European (non-Finnish)	0.000678%	147,493

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.Ser201=
Coding: c.603G>A
MANE Select: NM_002075
dbSNP: rs782790179
Type: single nucleotide variant
Location: chr12:6843882 (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

Similar variants

GNB3 p.Ser201Leu Uncertain significance ★ ⚠ same residue
GNB3 c.203+6G>A Uncertain significance ★★ same type
GNB3 p.Ala106Ser Uncertain significance ★★ ⚠ same type
GNB3 p.Ala231Thr Uncertain significance ★★ ⚠ same type
GNB3 p.Ala64Thr Uncertain significance ★★ ⚠ same type
GNB3 p.Arg129His Uncertain significance ★★ ⚠ same type
GNB3 p.Arg137Gln Uncertain significance ★★ ⚠ same type
GNB3 p.Arg150Cys 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-ser201 (accessed [today's date]).

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