Is GABRB3 p.Pro103Ser (c.307C>T) pathogenic?

GABRB3 p.Pro103Ser (c.307C>T) is classified Uncertain significance in GABRB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: likely benign (0.1254); Very rare (popmax 0.000169%, nfe); Associated with epilepsy, childhood absence, susceptibility to, 5.

What condition is associated with GABRB3 p.Pro103Ser (c.307C>T)?

GABRB3 p.Pro103Ser (c.307C>T) is associated with epilepsy, childhood absence, susceptibility to, 5, epilepsy, childhood absence, susceptibility to, 1 (ClinVar).

How common is GABRB3 p.Pro103Ser (c.307C>T) in the general population?

GABRB3 p.Pro103Ser (c.307C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about GABRB3 p.Pro103Ser (c.307C>T)?

AlphaMissense predicts likely benign (score 0.1254) — an in-silico prediction, not a clinical call.

GABRB3 p.Pro103Ser

c.307C>T · rs267604145 · VCV1355874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1254 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

epilepsy, childhood absence, susceptibility to, 5

Computational evidence

Protein change
AlphaMissense	0.1254	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -10.63	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 151 kb · p 1.9e-06 · regional, not allelic
Overall
CADD	25.4	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 0.000169% European (non-Finnish) · 2/1,179,982 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,996 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: GABRB3
Protein: p.Pro103Ser
Coding: c.307C>T
MANE Select: NM_000814
dbSNP: rs267604145
Type: single nucleotide variant
Location: chr15:26621468 (GRCh38)
Gene constraint: LOEUF 0.439 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 80.64 · 109 PDB

Full GABRB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epilepsy, childhood absence, susceptibility to, 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epilepsy, childhood absence, susceptibility to, 1

Similar variants

GABRB3 p.Pro103His Uncertain significance ★★ ⚠ same residue
GABRB3 p.Arg111Ter Pathogenic ★★ same condition
GABRB3 p.Arg194Ter Pathogenic ★★ same condition
GABRB3 p.Arg232Gln Pathogenic/Likely pathogenic ★★ same condition
GABRB3 p.Arg96Ser Pathogenic/Likely pathogenic ★★ same condition
GABRB3 p.Asp120Asn Pathogenic/Likely pathogenic ★★ same condition
GABRB3 p.Glu77Gln Likely pathogenic ★★ ⚠ same condition
GABRB3 p.Ile280Phe Likely pathogenic ★★ 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/gabrb3-p-pro103ser (accessed [today's date]).

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