Is GNAT2 p.Pro63Ser (c.187C>T) pathogenic?

GNAT2 p.Pro63Ser (c.187C>T) is classified Uncertain significance in GNAT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). AlphaMissense: likely benign (0.1085); Very rare (popmax 0.000339%, nfe).

How common is GNAT2 p.Pro63Ser (c.187C>T) in the general population?

GNAT2 p.Pro63Ser (c.187C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about GNAT2 p.Pro63Ser (c.187C>T)?

AlphaMissense predicts likely benign (score 0.1085) — an in-silico prediction, not a clinical call.

GNAT2 p.Pro63Ser

c.187C>T · rs1649750664 · VCV1059314

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1085 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1085	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP -0.038, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 9,513 bp · p 0.00023 · regional, not allelic
Overall
CADD	17.58	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,852 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,968 alleles · very rare exomes 4/1,461,698 · genomes 0/152,270 · joint denominator

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: GNAT2
Protein: p.Pro63Ser
Coding: c.187C>T
MANE Select: NM_001377295
dbSNP: rs1649750664
Type: single nucleotide variant
Location: chr1:109610156 (GRCh38)
Gene constraint: LOEUF 1.176 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.21 · 2 PDB
Residue 63: the g-alpha domain

Full GNAT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GNAT2 p.Arg105Ter Pathogenic/Likely pathogenic ★★ same type
GNAT2 p.Arg161Ter Pathogenic ★★ same type
GNAT2 p.Arg313Ter Pathogenic ★★ same type
GNAT2 p.Gln58Ter Pathogenic/Likely pathogenic ★★ same type
GNAT2 c.118+5G>A Uncertain significance ★★ same type
GNAT2 c.590+6T>C Uncertain significance ★★ same type
GNAT2 c.-53-78G>A Uncertain significance ★★ same type
GNAT2 p.Ala152Thr 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/gnat2-p-pro63ser (accessed [today's date]).

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