Is GABRD p.Ala368= (c.1104C>T) pathogenic?

GABRD p.Ala368= (c.1104C>T) is classified Benign in GABRD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Common (popmax 10.2%, eas) — too common for a highly-penetrant pathogenic allele; Associated with idiopathic generalized epilepsy.

What condition is associated with GABRD p.Ala368= (c.1104C>T)?

GABRD p.Ala368= (c.1104C>T) is associated with idiopathic generalized epilepsy (ClinVar).

GABRD p.Ala368=

Q: How common is GABRD p.Ala368= (c.1104C>T) in the general population?

GABRD p.Ala368= (c.1104C>T) is common (popmax 10.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1104C>T · rs28398772 · VCV460004

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 10.2%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.99 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.8
Overall
CADD	2.325	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.2% East Asian · 4,576/44,878 alleles

Filtering AF 9.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.85%

Overall 3.2% 51,667/1,612,650 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	10.2%	10
Finnishnot grpmax-eligible	6.32%	16
Ashkenazi Jewishnot grpmax-eligible	6.21%	16
Middle Eastern	4.44%	23
Remaining individualsnot grpmax-eligible	3.74%	27
Amishnot grpmax-eligible	3.51%	29
South Asian	3.37%	30
European (non-Finnish)	2.86%	35
Admixed American	2.44%	41
African / African-American	0.554%	180

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.Ala368=
Coding: c.1104C>T
MANE Select: NM_000815
dbSNP: rs28398772
Type: single nucleotide variant
Location: chr1:2030027 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 10 PDB

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-ala368 (accessed [today's date]).

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