Is GABBR2 p.Arg44Pro (c.131G>C) pathogenic?

GABBR2 p.Arg44Pro (c.131G>C) is classified Uncertain significance in GABBR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). AlphaMissense: likely benign (0.0924); Very rare (popmax 0.0016%, sas); Associated with Epileptic encephalopathy.

What condition is associated with GABBR2 p.Arg44Pro (c.131G>C)?

GABBR2 p.Arg44Pro (c.131G>C) is associated with Epileptic encephalopathy (ClinVar).

How common is GABBR2 p.Arg44Pro (c.131G>C) in the general population?

GABBR2 p.Arg44Pro (c.131G>C) is very rare (popmax 0.0016%, sas) (gnomAD).

What do computational predictors say about GABBR2 p.Arg44Pro (c.131G>C)?

AlphaMissense predicts likely benign (score 0.0924) — an in-silico prediction, not a clinical call.

GABBR2 p.Arg44Pro

c.131G>C · rs765018232 · VCV3010595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0924 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0016%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Epileptic encephalopathy

Computational evidence

Protein change
AlphaMissense	0.0924	likely benign
REVEL	0.398	indeterminate
SaProt	LLR -5.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 164 bp · p 0.69 · regional, not allelic
Overall
CADD	23.3	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 0.0016% South Asian · 1/62,676 alleles

Filtering AF 7.4e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.1e-05%

Overall 0.000286% 4/1,399,492 alleles · very rare exomes 4/1,248,058 · genomes 0/151,434 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0016%	62,676
European (non-Finnish)	0.000279%	357,870

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.Arg44Pro
Coding: c.131G>C
MANE Select: NM_005458
dbSNP: rs765018232
Type: single nucleotide variant
Location: chr9:98708607 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.00 · 26 PDB

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.Arg44= Likely benign ★ same residue
GABBR2 p.Arg44Gln Uncertain significance ★★ ⚠ 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-arg44pro (accessed [today's date]).

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