Is GNB3 p.Asp27= (c.81C>T) pathogenic?

GNB3 p.Asp27= (c.81C>T) is classified Benign/Likely benign in GNB3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Rare (popmax 0.59%, afr).

How common is GNB3 p.Asp27= (c.81C>T) in the general population?

GNB3 p.Asp27= (c.81C>T) is rare (popmax 0.59%, afr) (gnomAD).

GNB3 p.Asp27=

c.81C>T · rs145085793 · VCV748304

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.59%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.57	GERP -4.2, phastCons 0.01
Overall
CADD	7.931	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.59% African / African-American · 443/75,028 alleles

Filtering AF 0.545% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.527%

Overall 0.0328% 530/1,613,492 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.59%	169
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Admixed American	0.035%	2,856
South Asian	0.0187%	5,350
East Asian	0.00446%	22,432
European (non-Finnish)	0.00212%	47,186

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.Asp27=
Coding: c.81C>T
MANE Select: NM_002075
dbSNP: rs145085793
Type: single nucleotide variant
Location: chr12:6841609 (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.Asp27Gly 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-asp27 (accessed [today's date]).

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