Is GABBR2 p.Pro16= (c.48G>A) pathogenic?

GABBR2 p.Pro16= (c.48G>A) is classified Likely benign in GABBR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-22). Rare (popmax 0.12%, afr); Associated with Epileptic encephalopathy.

What condition is associated with GABBR2 p.Pro16= (c.48G>A)?

GABBR2 p.Pro16= (c.48G>A) is associated with Epileptic encephalopathy (ClinVar).

How common is GABBR2 p.Pro16= (c.48G>A) in the general population?

GABBR2 p.Pro16= (c.48G>A) is rare (popmax 0.12%, afr) (gnomAD).

GABBR2 p.Pro16=

c.48G>A · rs1023207573 · VCV720039

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.12%, 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 2.9	GERP 0.044, phastCons 1
Overall
CADD	12.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.12% African / African-American · 68/56,690 alleles

Filtering AF 0.097% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0887%

Overall 0.00799% 78/976,290 alleles · rare exomes 29/829,544 · genomes 49/146,746 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.12%	834
Remaining individualsnot grpmax-eligible	0.00665%	15,032
European (non-Finnish)	0.000981%	101,892

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.Pro16=
Coding: c.48G>A
MANE Select: NM_005458
dbSNP: rs1023207573
Type: single nucleotide variant
Location: chr9:98708690 (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.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-pro16 (accessed [today's date]).

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