Is GABRD p.Ser230= (c.690C>T) pathogenic?

GABRD p.Ser230= (c.690C>T) is classified Likely benign in GABRD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-16). Rare (popmax 0.499%, eas); Associated with idiopathic generalized epilepsy.

What condition is associated with GABRD p.Ser230= (c.690C>T)?

GABRD p.Ser230= (c.690C>T) is associated with idiopathic generalized epilepsy (ClinVar).

How common is GABRD p.Ser230= (c.690C>T) in the general population?

GABRD p.Ser230= (c.690C>T) is rare (popmax 0.499%, eas) (gnomAD).

GABRD p.Ser230=

c.690C>T · rs146193210 · VCV946905

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.499%, 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 -9.8
Overall
CADD	0.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.499% East Asian · 223/44,728 alleles

Filtering AF 0.445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.424%

Overall 0.0155% 250/1,610,124 alleles · rare exomes 236/1,457,940 · genomes 14/152,184 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.499%	201
Remaining individualsnot grpmax-eligible	0.0128%	7,790
Finnishnot grpmax-eligible	0.00799%	12,513
Admixed American	0.00668%	14,979
South Asian	0.0033%	30,302
African / African-American	0.00267%	37,462
European (non-Finnish)	0.000424%	235,712

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.Ser230=
Coding: c.690C>T
MANE Select: NM_000815
dbSNP: rs146193210
Type: single nucleotide variant
Location: chr1:2028291 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.82 · 10 PDB
Residue 230: 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-ser230 (accessed [today's date]).

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