Is GABBR2 p.Pro17= (c.51A>G) pathogenic?

GABBR2 p.Pro17= (c.51A>G) is classified Benign/Likely benign in GABBR2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-22). Rare (popmax 0.119%, afr); Associated with Epileptic encephalopathy.

What condition is associated with GABBR2 p.Pro17= (c.51A>G)?

GABBR2 p.Pro17= (c.51A>G) is associated with Epileptic encephalopathy (ClinVar).

How common is GABBR2 p.Pro17= (c.51A>G) in the general population?

GABBR2 p.Pro17= (c.51A>G) is rare (popmax 0.119%, afr) (gnomAD).

GABBR2 p.Pro17=

c.51A>G · rs893078508 · VCV720038

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.119%, 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 -4	GERP -2
Overall
CADD	10.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.119% African / African-American · 69/58,188 alleles

Filtering AF 0.0961% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0878%

Overall 0.0119% 127/1,066,010 alleles · rare exomes 67/920,694 · genomes 60/145,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.119%	843
East Asian	0.0652%	1,533
Remaining individualsnot grpmax-eligible	0.0144%	6,951
Admixed American	0.00542%	18,438
European (non-Finnish)	0.00475%	21,039

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.Pro17=
Coding: c.51A>G
MANE Select: NM_005458
dbSNP: rs893078508
Type: single nucleotide variant
Location: chr9:98708687 (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.Pro17_Pro20del 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
GABBR2 p.Arg48Trp 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-pro17 (accessed [today's date]).

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