Is GABRD p.Ser272= (c.816C>T) pathogenic?

GABRD p.Ser272= (c.816C>T) is classified Benign in GABRD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 40.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with idiopathic generalized epilepsy.

What condition is associated with GABRD p.Ser272= (c.816C>T)?

GABRD p.Ser272= (c.816C>T) is associated with idiopathic generalized epilepsy (ClinVar).

GABRD p.Ser272=

Q: How common is GABRD p.Ser272= (c.816C>T) in the general population?

GABRD p.Ser272= (c.816C>T) is common (popmax 40.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.816C>T · rs28408173 · VCV256825

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 40.3%, 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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.8
Overall
CADD	2.185	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 40.3% East Asian · 17,117/42,424 alleles

Filtering AF 39.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 39.6%

Overall 15% 234,734/1,569,906 alleles · common exomes 215,491/1,417,604 · genomes 19,243/152,302 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	40.3%	2
South Asian	24.9%	4
Admixed American	20.9%	5
Finnishnot grpmax-eligible	17.5%	6
Remaining individualsnot grpmax-eligible	15.7%	6
European (non-Finnish)	13.7%	7
Ashkenazi Jewishnot grpmax-eligible	11.5%	9
Middle Eastern	10.9%	9
Amishnot grpmax-eligible	10.6%	9
African / African-American	3.09%	32

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.Ser272=
Coding: c.816C>T
MANE Select: NM_000815
dbSNP: rs28408173
Type: single nucleotide variant
Location: chr1:2029235 (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-ser272 (accessed [today's date]).

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