Is GABRD p.Pro384Ser (c.1150C>T) pathogenic?

GABRD p.Pro384Ser (c.1150C>T) is classified Likely benign in GABRD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0749); Rare (popmax 0.891%, mid); Associated with idiopathic generalized epilepsy.

What condition is associated with GABRD p.Pro384Ser (c.1150C>T)?

GABRD p.Pro384Ser (c.1150C>T) is associated with idiopathic generalized epilepsy, intellectual disability (ClinVar).

How common is GABRD p.Pro384Ser (c.1150C>T) in the general population?

GABRD p.Pro384Ser (c.1150C>T) is rare (popmax 0.891%, mid) (gnomAD).

What do computational predictors say about GABRD p.Pro384Ser (c.1150C>T)?

AlphaMissense predicts likely benign (score 0.0749) — an in-silico prediction, not a clinical call.

GABRD p.Pro384Ser

c.1150C>T · rs79386457 · VCV460006

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0749 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.891%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

idiopathic generalized epilepsy

Computational evidence

Protein change
AlphaMissense	0.0749	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -5.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.69	phastCons 0.13
Regional constraint	o/e 1.00	unconstrained · MANE · 223 bp · p 0.98 · regional, not allelic
Overall
CADD	9.416	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.891% Middle Eastern · 54/6,060 alleles

Filtering AF 0.701% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.633%

Overall 0.0455% 732/1,608,874 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.891%	112
Ashkenazi Jewishnot grpmax-eligible	0.197%	507
Remaining individualsnot grpmax-eligible	0.103%	973
Admixed American	0.0945%	1,059
South Asian	0.0597%	1,676
European (non-Finnish)	0.0362%	2,759
African / African-American	0.0241%	4,157
East Asian	0.00223%	44,868

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.Pro384Ser
Coding: c.1150C>T
MANE Select: NM_000815
dbSNP: rs79386457
Type: single nucleotide variant
Location: chr1:2030073 (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

Also linked: intellectual disability

Similar variants

GABRD p.Pro384= Likely benign ★★ same residue
GABRD p.Pro384Leu Uncertain significance ★ ⚠ same residue
GABRD p.Pro384Ala Uncertain significance ★ ⚠ same residue
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

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-pro384ser (accessed [today's date]).

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