Is GNB3 p.Ile80= (c.240C>T) pathogenic?

GNB3 p.Ile80= (c.240C>T) is classified Likely benign in GNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-03). Very rare (popmax 0.0078%, nfe).

How common is GNB3 p.Ile80= (c.240C>T) in the general population?

GNB3 p.Ile80= (c.240C>T) is very rare (popmax 0.0078%, nfe) (gnomAD).

GNB3 p.Ile80=

c.240C>T · rs190325696 · VCV1626337

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0078%, nfe)

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 -3.9	GERP -4.5
Overall
CADD	8.604	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0078% European (non-Finnish) · 92/1,179,882 alleles

Filtering AF 0.00648% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.006%

Overall 0.00601% 97/1,613,808 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0078%	12,825
Admixed American	0.00333%	30,000
Remaining individualsnot grpmax-eligible	0.0032%	31,240
South Asian	0.0011%	91,082

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.Ile80=
Coding: c.240C>T
MANE Select: NM_002075
dbSNP: rs190325696
Type: single nucleotide variant
Location: chr12:6843210 (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 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
GNB3 p.Arg42Gln 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-ile80 (accessed [today's date]).

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