What condition is associated with GABRB1 p.Arg53Trp (c.157C>T)?

GABRB1 p.Arg53Trp (c.157C>T) is associated with developmental and epileptic encephalopathy, 45 (ClinVar).

How common is GABRB1 p.Arg53Trp (c.157C>T) in the general population?

GABRB1 p.Arg53Trp (c.157C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GABRB1 p.Arg53Trp (c.157C>T)?

AlphaMissense predicts likely pathogenic (score 0.9972) — an in-silico prediction, not a clinical call.

GABRB1 p.Arg53Trp

Q: Is GABRB1 p.Arg53Trp (c.157C>T) pathogenic?

GABRB1 p.Arg53Trp (c.157C>T) is classified Likely pathogenic in GABRB1 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9972); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 45.

Q: How is Non-specific early-onset epileptic encephalopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.157C>T · rs1135401786 · VCV431076

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9972 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 45

Computational evidence

Protein change
AlphaMissense	0.9972	likely pathogenic ✓ concordant with ClinVar
REVEL	0.8	moderately pathogenic-leaning
SaProt	LLR -15.72	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 3.3	GERP -0.82, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 371 kb · p 5.3e-10 · regional, not allelic
Overall
CADD	31.0	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: GABRB1
Protein: p.Arg53Trp
Coding: c.157C>T
MANE Select: NM_000812
dbSNP: rs1135401786
Type: single nucleotide variant
Location: chr4:47031990 (GRCh38)
Gene constraint: LOEUF 0.565 · pLI 0.73 (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 3 PDB

Full GABRB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 45 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific early-onset epileptic encephalopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Not applicable
Onset: Infancy, Neonatal

Similar variants

GABRB1 p.Arg53Leu Uncertain significance ★ ⚠ same residue
GABRB1 p.Arg405His Uncertain significance ★★ ⚠ same condition
GABRB1 p.Asp345His Uncertain significance ★★ ⚠ same condition
GABRB1 p.Pro103Ser Uncertain significance ★★ ⚠ same condition
GABRB1 p.Ser370Gly Uncertain significance ★★ ⚠ same condition
GABRB1 p.Ser381Leu Uncertain significance ★★ ⚠ same condition
GABRB1 p.Thr282= Benign ★★ same condition
GABRB1 p.Ile247Thr 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/gabrb1-p-arg53trp (accessed [today's date]).

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