Is GABRD p.Ala438= (c.1314G>A) pathogenic?

GABRD p.Ala438= (c.1314G>A) is classified Likely benign in GABRD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). Ultra-rare (popmax 0.0259%, afr); Associated with idiopathic generalized epilepsy.

What condition is associated with GABRD p.Ala438= (c.1314G>A)?

GABRD p.Ala438= (c.1314G>A) is associated with idiopathic generalized epilepsy (ClinVar).

How common is GABRD p.Ala438= (c.1314G>A) in the general population?

GABRD p.Ala438= (c.1314G>A) is ultra-rare (popmax 0.0259%, afr) (gnomAD).

GABRD p.Ala438=

c.1314G>A · rs138909980 · VCV1143015

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0259%, afr)

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -4.8
Overall
CADD	4.323	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0259% African / African-American · 19/73,422 alleles

Filtering AF 0.0169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.014%

Overall 0.00211% 33/1,563,080 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0259%	3,864
Finnishnot grpmax-eligible	0.00651%	15,365
South Asian	0.00234%	42,678
Admixed American	0.00185%	54,038
European (non-Finnish)	0.000608%	164,371

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: GABRD
Protein: p.Ala438=
Coding: c.1314G>A
MANE Select: NM_000815
dbSNP: rs138909980
Type: single nucleotide variant
Location: chr1:2030237 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 10 PDB
Residue 438: an α-helix

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

Disease context

idiopathic generalized epilepsy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GABRD p.Pro257Leu Likely pathogenic ★★ same condition
GABRD p.Ala24Val Uncertain significance ★★ ⚠ same condition
GABRD p.Ala331Gly Uncertain significance ★★ ⚠ same condition
GABRD p.Ala437Val Uncertain significance ★★ ⚠ same condition
GABRD p.Arg23Gly Uncertain significance ★★ ⚠ same condition
GABRD p.Arg244Trp Uncertain significance ★★ ⚠ same condition
GABRD p.Arg378His Uncertain significance ★★ ⚠ same condition
GABRD p.Arg379Pro Uncertain significance ★★ ⚠ 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/gabrd-p-ala438 (accessed [today's date]).

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