Is GABRB3 p.Pro301Ser (c.901C>T) pathogenic?

GABRB3 p.Pro301Ser (c.901C>T) is classified Pathogenic in GABRB3 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.8844); Absent from gnomAD v4.1; Associated with Neurodevelopmental delay.

What condition is associated with GABRB3 p.Pro301Ser (c.901C>T)?

GABRB3 p.Pro301Ser (c.901C>T) is associated with Neurodevelopmental delay, epilepsy, childhood absence, susceptibility to, 5 (ClinVar).

How common is GABRB3 p.Pro301Ser (c.901C>T) in the general population?

GABRB3 p.Pro301Ser (c.901C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GABRB3 p.Pro301Ser (c.901C>T)?

AlphaMissense predicts likely pathogenic (score 0.8844) — an in-silico prediction, not a clinical call.

GABRB3 p.Pro301Ser

c.901C>T · rs1889966666 · VCV975243

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8844 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Neurodevelopmental delay

Computational evidence

Protein change
AlphaMissense	0.8844	likely pathogenic ✓ concordant with ClinVar
REVEL	0.362	indeterminate
SaProt	LLR -3.13	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.22	constrained · MANE · 19 kb · p 1.7e-21 · regional, not allelic
Overall
CADD	25.9	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: GABRB3
Protein: p.Pro301Ser
Coding: c.901C>T
MANE Select: NM_000814
dbSNP: rs1889966666
Type: single nucleotide variant
Location: chr15:26561111 (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

Neurodevelopmental delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epilepsy, childhood absence, susceptibility to, 5

Similar variants

GABRB3 p.Pro301Leu Likely pathogenic ★★ same residue
GABRB3 p.Pro301_Tyr302insPheAsnThrHisLeuArgGluThrLeuProLysIlePro Likely pathogenic ★ same residue
GABRB3 p.Pro301Ala 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

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-pro301ser (accessed [today's date]).

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