Is GABRR2 p.Arg287Cys (c.859C>T) pathogenic?

GABRR2 p.Arg287Cys (c.859C>T) is classified Uncertain significance in GABRR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: ambiguous (0.5083); Ultra-rare (popmax 0.0156%, eas).

How common is GABRR2 p.Arg287Cys (c.859C>T) in the general population?

GABRR2 p.Arg287Cys (c.859C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about GABRR2 p.Arg287Cys (c.859C>T)?

AlphaMissense predicts ambiguous (score 0.5083) — an in-silico prediction, not a clinical call.

GABRR2 p.Arg287Cys

c.859C>T · rs575098710 · VCV2607768

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5083 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Computational evidence

Protein change
AlphaMissense	0.5083	ambiguous
REVEL	0.511	indeterminate
SaProt	LLR -11.18	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.96, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 57 kb · p 0.76 · regional, not allelic
Overall
CADD	29.0	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

Grpmax group 0.0156% East Asian · 7/44,882 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00118% 19/1,614,098 alleles · ultra-rare exomes 15/1,461,822 · genomes 4/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,412
Admixed American	0.00333%	30,012
European (non-Finnish)	0.000847%	118,000

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: GABRR2
Protein: p.Arg287Cys
Coding: c.859C>T
MANE Select: NM_002043
dbSNP: rs575098710
Type: single nucleotide variant
Location: chr6:89265643 (GRCh38)
Gene constraint: LOEUF 1.005 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.00

Full GABRR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GABRR2 p.Arg287His Likely benign ★ same residue
GABRR2 c.-26C>A Uncertain significance ★ same type
GABRR2 c.-50C>G Uncertain significance ★ same type
GABRR2 c.-53G>T Uncertain significance ★ same type
GABRR2 c.-59G>A Uncertain significance ★ same type
GABRR2 c.-59G>T Uncertain significance ★ same type
GABRR2 c.-71T>A Uncertain significance ★ same type
GABRR2 p.Ala200Val Uncertain significance ★ ⚠ same type

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/gabrr2-p-arg287cys (accessed [today's date]).

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