Is GNB3 p.Ser147Tyr (c.440C>A) pathogenic?

GNB3 p.Ser147Tyr (c.440C>A) is classified Uncertain significance in GNB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely pathogenic (0.9987); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GNB3 p.Ser147Tyr (c.440C>A)?

GNB3 p.Ser147Tyr (c.440C>A) is associated with Inborn genetic diseases (ClinVar).

How common is GNB3 p.Ser147Tyr (c.440C>A) in the general population?

GNB3 p.Ser147Tyr (c.440C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GNB3 p.Ser147Tyr (c.440C>A)?

AlphaMissense predicts likely pathogenic (score 0.9987) — an in-silico prediction, not a clinical call.

GNB3 p.Ser147Tyr

c.440C>A · rs782199265 · VCV3100603

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9987	likely pathogenic
REVEL	0.539	indeterminate
SaProt	LLR -16.32	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 5,607 bp · p 0.03 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Ser147Tyr
Coding: c.440C>A
MANE Select: NM_002075
dbSNP: rs782199265
Type: single nucleotide variant
Location: chr12:6843641 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GNB3 p.Ser147= Likely benign ★ same residue
GNB3 p.Ala106Ser Uncertain significance ★★ ⚠ same condition
GNB3 p.Ala231Thr Uncertain significance ★★ ⚠ same condition
GNB3 p.Ala64Thr Uncertain significance ★★ ⚠ same condition
GNB3 p.Arg129His Uncertain significance ★★ ⚠ same condition
GNB3 p.Arg150Cys Uncertain significance ★★ ⚠ same condition
GNB3 p.Arg8His Uncertain significance ★★ ⚠ same condition
GNB3 p.Arg96His Uncertain significance ★★ ⚠ same condition

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-ser147tyr (accessed [today's date]).

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