Is GABBR2 p.Pro4= (c.12G>C) pathogenic?

GABBR2 p.Pro4= (c.12G>C) is classified Likely benign in GABBR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-17). Very rare (popmax 0.00048%, nfe); Associated with Epileptic encephalopathy.

What condition is associated with GABBR2 p.Pro4= (c.12G>C)?

GABBR2 p.Pro4= (c.12G>C) is associated with Epileptic encephalopathy (ClinVar).

How common is GABBR2 p.Pro4= (c.12G>C) in the general population?

GABBR2 p.Pro4= (c.12G>C) is very rare (popmax 0.00048%, nfe) (gnomAD).

GABBR2 p.Pro4=

c.12G>C · rs1830938419 · VCV1646546

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00048%, nfe)

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 3.3	GERP 1.1, phastCons 1
Overall
CADD	13.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00048% European (non-Finnish) · 4/834,136 alleles

Filtering AF 0.000112% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.6e-05%

Overall 0.000405% 4/988,118 alleles · very rare exomes 4/844,154 · genomes 0/143,964 · joint denominator

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.Pro4=
Coding: c.12G>C
MANE Select: NM_005458
dbSNP: rs1830938419
Type: single nucleotide variant
Location: chr9:98708726 (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.Pro4Gln Uncertain significance ★ ⚠ same residue
GABBR2 p.Pro4Leu Uncertain significance ★ ⚠ same residue
GABBR2 p.Pro4Thr 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

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-pro4 (accessed [today's date]).

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