Is GABRB1 p.Pro103Ser (c.307C>T) pathogenic?

GABRB1 p.Pro103Ser (c.307C>T) is classified Uncertain significance in GABRB1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-11-03). AlphaMissense: likely benign (0.1687); Very rare (popmax 8.48e-05%, nfe); Associated with developmental and epileptic encephalopathy, 45.

What condition is associated with GABRB1 p.Pro103Ser (c.307C>T)?

GABRB1 p.Pro103Ser (c.307C>T) is associated with developmental and epileptic encephalopathy, 45 (ClinVar).

How common is GABRB1 p.Pro103Ser (c.307C>T) in the general population?

GABRB1 p.Pro103Ser (c.307C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about GABRB1 p.Pro103Ser (c.307C>T)?

AlphaMissense predicts likely benign (score 0.1687) — an in-silico prediction, not a clinical call.

GABRB1 p.Pro103Ser

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.307C>T · rs775749394 · VCV638346

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1687 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 45

Computational evidence

Protein change
AlphaMissense	0.1687	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -8.82	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 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 371 kb · p 5.3e-10 · regional, not allelic
Overall
CADD	24.2	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 8.48e-05% European (non-Finnish) · 1/1,179,220 alleles

Overall 6.85e-05% 1/1,460,670 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: GABRB1
Protein: p.Pro103Ser
Coding: c.307C>T
MANE Select: NM_000812
dbSNP: rs775749394
Type: single nucleotide variant
Location: chr4:47161315 (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.Arg405His Uncertain significance ★★ ⚠ same condition
GABRB1 p.Asp345His 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.Arg53Trp Likely pathogenic ★ same condition
GABRB1 p.Ile247Thr Likely pathogenic ★ same condition
GABRB1 p.Thr285Lys 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-pro103ser (accessed [today's date]).

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