Is GABRG2 p.Pro83Ser (c.247C>T) pathogenic?

GABRG2 p.Pro83Ser (c.247C>T) is classified Pathogenic in GABRG2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-05-09). AlphaMissense: likely pathogenic (0.9995); Very rare (popmax 8.48e-05%, nfe).

How common is GABRG2 p.Pro83Ser (c.247C>T) in the general population?

GABRG2 p.Pro83Ser (c.247C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about GABRG2 p.Pro83Ser (c.247C>T)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

GABRG2 p.Pro83Ser

c.247C>T · rs587777365 · VCV127233

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic ✓ concordant with ClinVar · top 3% in GABRG2
REVEL	0.975	strongly pathogenic-leaning
SaProt	LLR -13.59	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 10 kb · p 3.4e-13 · regional, not allelic
Overall
CADD	29.3	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,400 alleles

Overall 6.84e-05% 1/1,460,962 alleles · very rare

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: GABRG2
Protein: p.Pro83Ser
Coding: c.247C>T
MANE Select: NM_198904
dbSNP: rs587777365
Type: single nucleotide variant
Location: chr5:162093967 (GRCh38)
Gene constraint: LOEUF 0.428 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 77.41 · 84 PDB
Residue 83: a UniProt-annotated variant site (found in a patient with idiopathic generalized epilepsy; uncertain significance; the currents elicited by mutant receptors are indistinguishable from wild-type; no difference in sensitivity of the mutant receptors to the allosteric regulators zinc and benzodiazepine diazepam compared to wild-type); a turn

Full GABRG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GABRG2 p.Pro83Leu Likely pathogenic ★ same residue
GABRG2 p.Pro83Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
GABRG2 c.259+1G>A Pathogenic/Likely pathogenic ★★ same type
GABRG2 p.Ala106Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
GABRG2 p.Arg136Ter Pathogenic ★★ same type
GABRG2 p.Arg177Ter Pathogenic/Likely pathogenic ★★ same type
GABRG2 p.Arg224Ter Pathogenic/Likely pathogenic ★★ same type
GABRG2 p.Arg323Gln Pathogenic ★★ 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/gabrg2-p-pro83ser (accessed [today's date]).

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