Is GABBR2 p.Pro643Ser (c.1927C>T) pathogenic?

GABBR2 p.Pro643Ser (c.1927C>T) is classified Likely benign in GABBR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-07). AlphaMissense: likely pathogenic (0.9847); Absent from gnomAD v4.1; Associated with Epileptic encephalopathy.

What condition is associated with GABBR2 p.Pro643Ser (c.1927C>T)?

GABBR2 p.Pro643Ser (c.1927C>T) is associated with Epileptic encephalopathy (ClinVar).

How common is GABBR2 p.Pro643Ser (c.1927C>T) in the general population?

GABBR2 p.Pro643Ser (c.1927C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GABBR2 p.Pro643Ser (c.1927C>T)?

AlphaMissense predicts likely pathogenic (score 0.9847) — an in-silico prediction, not a clinical call.

GABBR2 p.Pro643Ser

c.1927C>T · rs2491221528 · VCV2000540

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9847 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Epileptic encephalopathy

Computational evidence

Protein change
AlphaMissense	0.9847	likely pathogenic
REVEL	0.843	moderately pathogenic-leaning
SaProt	LLR -12.26	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 52 kb · p 0.0012 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GABBR2
Protein: p.Pro643Ser
Coding: c.1927C>T
MANE Select: NM_005458
dbSNP: rs2491221528
Type: single nucleotide variant
Location: chr9:98311172 (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-pro643ser (accessed [today's date]).

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