Is GABBR2 p.Ser461= (c.1383C>T) pathogenic?

GABBR2 p.Ser461= (c.1383C>T) is classified Benign in GABBR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-21). Rare (popmax 0.161%, afr); Associated with Epileptic encephalopathy.

What condition is associated with GABBR2 p.Ser461= (c.1383C>T)?

GABBR2 p.Ser461= (c.1383C>T) is associated with Epileptic encephalopathy (ClinVar).

How common is GABBR2 p.Ser461= (c.1383C>T) in the general population?

GABBR2 p.Ser461= (c.1383C>T) is rare (popmax 0.161%, afr) (gnomAD).

GABBR2 p.Ser461=

c.1383C>T · rs55677951 · VCV772574

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.161%, afr)

Conditions

Epileptic encephalopathy

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 -3.4	GERP -4.2
Overall
CADD	7.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.161% African / African-American · 121/74,950 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.00881% 142/1,611,756 alleles · rare exomes 72/1,459,590 · genomes 70/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.161%	619
Admixed American	0.0117%	8,546
Remaining individualsnot grpmax-eligible	0.00961%	10,404
East Asian	0.00892%	11,205
European (non-Finnish)	0.000339%	294,684

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: GABBR2
Protein: p.Ser461=
Coding: c.1383C>T
MANE Select: NM_005458
dbSNP: rs55677951
Type: single nucleotide variant
Location: chr9:98389000 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.00 · 26 PDB
Residue 461: a β-strand

Full GABBR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Epileptic encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GABBR2 p.Gly693Trp Pathogenic ★★ same condition
GABBR2 p.Ala444Thr Uncertain significance ★★ ⚠ same condition
GABBR2 p.Ala580Ser Uncertain significance ★★ ⚠ same condition
GABBR2 p.Ala69Pro Uncertain significance ★★ ⚠ same condition
GABBR2 p.Ala708Ser Uncertain significance ★★ ⚠ same condition
GABBR2 p.Arg301His Uncertain significance ★★ ⚠ same condition
GABBR2 p.Arg48Trp Uncertain significance ★★ ⚠ same condition
GABBR2 p.Arg637Gln 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/gabbr2-p-ser461 (accessed [today's date]).

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