Is GABRD p.Ala49= (c.147C>T) pathogenic?

GABRD p.Ala49= (c.147C>T) is classified Likely benign in GABRD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-30). Ultra-rare (popmax 0.0329%, mid); Associated with idiopathic generalized epilepsy.

What condition is associated with GABRD p.Ala49= (c.147C>T)?

GABRD p.Ala49= (c.147C>T) is associated with idiopathic generalized epilepsy (ClinVar).

How common is GABRD p.Ala49= (c.147C>T) in the general population?

GABRD p.Ala49= (c.147C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

GABRD p.Ala49=

c.147C>T · rs147463074 · VCV374418

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

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 -0.4	phastCons 0.004
Overall
CADD	5.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,080 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00415% 67/1,612,554 alleles · ultra-rare exomes 61/1,460,290 · genomes 6/152,264 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,040
East Asian	0.0312%	3,207
Admixed American	0.0167%	6,000
African / African-American	0.00667%	14,989
Remaining individualsnot grpmax-eligible	0.00641%	15,609
South Asian	0.00329%	30,364
European (non-Finnish)	0.00246%	40,683

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.Ala49=
Coding: c.147C>T
MANE Select: NM_000815
dbSNP: rs147463074
Type: single nucleotide variant
Location: chr1:2025020 (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-ala49 (accessed [today's date]).

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