Is GABRD p.Val249= (c.747G>A) pathogenic?

GABRD p.Val249= (c.747G>A) is classified Likely benign in GABRD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). Very rare (popmax 0.00242%, eas); Associated with idiopathic generalized epilepsy.

What condition is associated with GABRD p.Val249= (c.747G>A)?

GABRD p.Val249= (c.747G>A) is associated with idiopathic generalized epilepsy (ClinVar).

How common is GABRD p.Val249= (c.747G>A) in the general population?

GABRD p.Val249= (c.747G>A) is very rare (popmax 0.00242%, eas) (gnomAD).

GABRD p.Val249=

c.747G>A · rs199993714 · VCV1140118

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00242%, eas)

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 0.74	phastCons 1
Overall
CADD	8.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00242% East Asian · 1/41,298 alleles

Filtering AF 0.000368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000267%

Overall 0.000644% 10/1,553,934 alleles · very rare exomes 9/1,401,556 · genomes 1/152,378 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00242%	41,298
European (non-Finnish)	0.000782%	127,865

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.Val249=
Coding: c.747G>A
MANE Select: NM_000815
dbSNP: rs199993714
Type: single nucleotide variant
Location: chr1:2029166 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 10 PDB
Residue 249: 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-val249 (accessed [today's date]).

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