Is GNB3 p.Ala206Asp (c.617C>A) pathogenic?

GNB3 p.Ala206Asp (c.617C>A) is classified Uncertain significance in GNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-09). AlphaMissense: likely pathogenic (0.9741); Absent from gnomAD v4.1.

How common is GNB3 p.Ala206Asp (c.617C>A) in the general population?

GNB3 p.Ala206Asp (c.617C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GNB3 p.Ala206Asp (c.617C>A)?

AlphaMissense predicts likely pathogenic (score 0.9741) — an in-silico prediction, not a clinical call.

GNB3 p.Ala206Asp

c.617C>A · rs2542352101 · VCV2095449

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9741 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9741	likely pathogenic
REVEL	0.208	benign-leaning
SaProt	LLR -14.97	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 5,607 bp · p 0.03 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GNB3
Protein: p.Ala206Asp
Coding: c.617C>A
MANE Select: NM_002075
dbSNP: rs2542352101
Type: single nucleotide variant
Location: chr12:6843896 (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-ala206asp (accessed [today's date]).

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