Is GABRB2 p.Phe393Ser (c.1178T>C) pathogenic?

GABRB2 p.Phe393Ser (c.1178T>C) is classified Benign in GABRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). AlphaMissense: likely benign (0.1164); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with GABRB2 p.Phe393Ser (c.1178T>C)?

GABRB2 p.Phe393Ser (c.1178T>C) is associated with intellectual disability (ClinVar).

How common is GABRB2 p.Phe393Ser (c.1178T>C) in the general population?

GABRB2 p.Phe393Ser (c.1178T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GABRB2 p.Phe393Ser (c.1178T>C)?

AlphaMissense predicts likely benign (score 0.1164) — an in-silico prediction, not a clinical call.

GABRB2 p.Phe393Ser

c.1178T>C · rs2113389282 · VCV1544216

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1164 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.1164	likely benign
REVEL	0.291	indeterminate
SaProt	LLR -2.31	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 37 kb · p 0.073 · regional, not allelic
Overall
CADD	23.2	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: GABRB2
Protein: p.Phe393Ser
Coding: c.1178T>C
MANE Select: NM_001371727
dbSNP: rs2113389282
Type: single nucleotide variant
Location: chr5:161326381 (GRCh38)
Gene constraint: LOEUF 0.426 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.65 · 31 PDB

Full GABRB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GABRB2 p.Ala304Val Pathogenic/Likely pathogenic ★★ same condition
GABRB2 p.Arg293Trp Pathogenic/Likely pathogenic ★★ same condition
GABRB2 p.Asp125Asn Pathogenic ★★ same condition
GABRB2 p.Ile288Thr Likely pathogenic ★★ same condition
GABRB2 p.Phe245Leu Pathogenic/Likely pathogenic ★★ same condition
GABRB2 p.Thr284Ile Pathogenic/Likely pathogenic ★★ same condition
GABRB2 p.Tyr301Cys Pathogenic/Likely pathogenic ★★ same condition
GABRB2 p.Tyr301Phe 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/gabrb2-p-phe393ser (accessed [today's date]).

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