Is GABRD p.Ala129= (c.387C>A) pathogenic?

GABRD p.Ala129= (c.387C>A) is classified Likely benign in GABRD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). Very rare (popmax 0.000339%, nfe); Associated with idiopathic generalized epilepsy.

What condition is associated with GABRD p.Ala129= (c.387C>A)?

GABRD p.Ala129= (c.387C>A) is associated with idiopathic generalized epilepsy (ClinVar).

How common is GABRD p.Ala129= (c.387C>A) in the general population?

GABRD p.Ala129= (c.387C>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

GABRD p.Ala129=

c.387C>A · rs1277746264 · VCV1127044

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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 3.3	phastCons 1
Overall
CADD	11.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,008 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,046 alleles · very rare exomes 4/1,460,680 · genomes 0/152,366 · joint denominator

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.Ala129=
Coding: c.387C>A
MANE Select: NM_000815
dbSNP: rs1277746264
Type: single nucleotide variant
Location: chr1:2025655 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 10 PDB
Residue 129: a β-strand

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-ala129 (accessed [today's date]).

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