Is GABRA5 p.Ser413Phe (c.1238C>T) pathogenic?

GABRA5 p.Ser413Phe (c.1238C>T) is classified Pathogenic in GABRA5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-11-25). AlphaMissense: likely benign (0.1015); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy, 79.

What condition is associated with GABRA5 p.Ser413Phe (c.1238C>T)?

GABRA5 p.Ser413Phe (c.1238C>T) is associated with developmental and epileptic encephalopathy, 79 (ClinVar).

How common is GABRA5 p.Ser413Phe (c.1238C>T) in the general population?

GABRA5 p.Ser413Phe (c.1238C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GABRA5 p.Ser413Phe (c.1238C>T)?

AlphaMissense predicts likely benign (score 0.1015) — an in-silico prediction, not a clinical call.

GABRA5 p.Ser413Phe

c.1238C>T · rs1595441329 · VCV689393

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1015 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 79

Computational evidence

Protein change
AlphaMissense	0.1015	likely benign ⚠ discordant with ClinVar
REVEL	0.182	moderately benign-leaning
SaProt	LLR -9.02	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 5.5	GERP 8.3, phastCons 0.66
Regional constraint	o/e 0.81	unconstrained · MANE · 4,823 bp · p 0.033 · regional, not allelic
Overall
CADD	21.4	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

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: GABRA5
Protein: p.Ser413Phe
Coding: c.1238C>T
MANE Select: NM_000810
dbSNP: rs1595441329
Type: single nucleotide variant
Location: chr15:26948082 (GRCh38)
Gene constraint: LOEUF 0.56 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 81.67 · 23 PDB
Residue 413: a UniProt-annotated variant site (in dee79; decreased subcellular localization to the cell membrane resulting in altered protein localization to the synapse and altered gamma-aminobutyric acid signaling pathway; the mutant subunit decreases the trafficking of the partnering gabrb3 subunit to the cell membrane with no effect on other subunits)

Full GABRA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 79 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GABRA5 p.Thr301Arg Pathogenic/Likely pathogenic ★★ same condition
GABRA5 p.Val294Phe Pathogenic/Likely pathogenic ★★ same condition
GABRA5 p.Arg283Trp Uncertain significance ★★ ⚠ same condition
GABRA5 p.Ser238Asn Uncertain significance ★★ ⚠ same condition
GABRA5 p.Ser333Leu Uncertain significance ★★ ⚠ same condition
GABRA5 c.878-27T>A Benign ★★ same condition
GABRA5 c.878-9C>A Benign ★★ same condition
GABRA5 p.Ala195= Benign/Likely benign ★★ 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/gabra5-p-ser413phe (accessed [today's date]).

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