Is GABBR2 p.Pro55Ser (c.163C>T) pathogenic?

GABBR2 p.Pro55Ser (c.163C>T) is classified Uncertain significance in GABBR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-11). AlphaMissense: likely benign (0.1169); Very rare (popmax 0.0014%, afr); Associated with Epileptic encephalopathy.

What condition is associated with GABBR2 p.Pro55Ser (c.163C>T)?

GABBR2 p.Pro55Ser (c.163C>T) is associated with Epileptic encephalopathy (ClinVar).

How common is GABBR2 p.Pro55Ser (c.163C>T) in the general population?

GABBR2 p.Pro55Ser (c.163C>T) is very rare (popmax 0.0014%, afr) (gnomAD).

What do computational predictors say about GABBR2 p.Pro55Ser (c.163C>T)?

AlphaMissense predicts likely benign (score 0.1169) — an in-silico prediction, not a clinical call.

GABBR2 p.Pro55Ser

c.163C>T · rs2490288447 · VCV2010256

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1169 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0014%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Epileptic encephalopathy

Computational evidence

Protein change
AlphaMissense	0.1169	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.80	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 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 164 bp · p 0.69 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0014% African / African-American · 1/71,268 alleles

Overall 0.000131% 2/1,525,450 alleles · very rare exomes 2/1,373,352 · genomes 0/152,098 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0014%	71,268
South Asian	0.00125%	80,282

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.Pro55Ser
Coding: c.163C>T
MANE Select: NM_005458
dbSNP: rs2490288447
Type: single nucleotide variant
Location: chr9:98708575 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.00 · 26 PDB
Residue 55: 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.Pro55Arg Uncertain significance ★ ⚠ same residue
GABBR2 p.Pro55= Likely benign ★ same residue
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

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-pro55ser (accessed [today's date]).

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