Is GABBR2 p.Pro335= (c.1005A>G) pathogenic?

GABBR2 p.Pro335= (c.1005A>G) is classified Likely benign in GABBR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-27). Ultra-rare (popmax 0.0121%, sas); Associated with Epileptic encephalopathy.

What condition is associated with GABBR2 p.Pro335= (c.1005A>G)?

GABBR2 p.Pro335= (c.1005A>G) is associated with Epileptic encephalopathy (ClinVar).

How common is GABBR2 p.Pro335= (c.1005A>G) in the general population?

GABBR2 p.Pro335= (c.1005A>G) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

GABBR2 p.Pro335=

c.1005A>G · rs112301334 · VCV1589024

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

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 -4.1	GERP -5.3
Overall
CADD	5.114	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/90,974 alleles

Filtering AF 0.00677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.000994% 16/1,609,626 alleles · ultra-rare exomes 16/1,457,330 · genomes 0/152,296 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,270
Remaining individualsnot grpmax-eligible	0.00642%	15,587
African / African-American	0.00133%	74,952

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.Pro335=
Coding: c.1005A>G
MANE Select: NM_005458
dbSNP: rs112301334
Type: single nucleotide variant
Location: chr9:98454212 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.00 · 26 PDB
Residue 335: 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-pro335 (accessed [today's date]).

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