Is GABBR2 p.Pro161= (c.483T>C) pathogenic?

GABBR2 p.Pro161= (c.483T>C) is classified Benign in GABBR2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Common (popmax 15.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Epileptic encephalopathy.

What condition is associated with GABBR2 p.Pro161= (c.483T>C)?

GABBR2 p.Pro161= (c.483T>C) is associated with Epileptic encephalopathy (ClinVar).

GABBR2 p.Pro161=

Q: How common is GABBR2 p.Pro161= (c.483T>C) in the general population?

GABBR2 p.Pro161= (c.483T>C) is common (popmax 15.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.483T>C · rs35449008 · VCV462139

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 15.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Epileptic encephalopathy

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 -0.67	GERP -2.7
Overall
CADD	7.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.9% African / African-American · 11,953/75,014 alleles

Filtering AF 15.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.6%

Overall 3.68% 59,456/1,614,052 alleles · common exomes 49,468/1,461,738 · genomes 9,988/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	15.9%	6
Remaining individualsnot grpmax-eligible	3.59%	28
Finnishnot grpmax-eligible	3.41%	29
European (non-Finnish)	3.39%	29
Middle Eastern	2.46%	41
Admixed American	2.21%	45
Ashkenazi Jewishnot grpmax-eligible	2.1%	48
South Asian	1.07%	94
Amishnot grpmax-eligible	0.329%	304

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.Pro161=
Coding: c.483T>C
MANE Select: NM_005458
dbSNP: rs35449008
Type: single nucleotide variant
Location: chr9:98542020 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.00 · 26 PDB
Residue 161: an α-helix

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-pro161 (accessed [today's date]).

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