Is GRID2 p.Arg280Lys (c.839G>A) pathogenic?

GRID2 p.Arg280Lys (c.839G>A) is classified Uncertain significance in GRID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-02). AlphaMissense: likely pathogenic (0.7473); No allele count reported in gnomAD v4.1 (AN 1,612,452); Associated with Inborn genetic diseases.

What condition is associated with GRID2 p.Arg280Lys (c.839G>A)?

GRID2 p.Arg280Lys (c.839G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GRID2 p.Arg280Lys (c.839G>A) in the general population?

GRID2 p.Arg280Lys (c.839G>A) is no allele count reported in gnomAD v4.1 (AN 1,612,452) (gnomAD).

What do computational predictors say about GRID2 p.Arg280Lys (c.839G>A)?

AlphaMissense predicts likely pathogenic (score 0.7473) — an in-silico prediction, not a clinical call.

GRID2 p.Arg280Lys

c.839G>A · VCV4621129

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7473 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,452)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7473	likely pathogenic
REVEL	0.712	pathogenic-leaning
SaProt	LLR -5.71	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 920 kb · p 0.22 · regional, not allelic
Overall
CADD	25.0	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

No allele count reported in gnomAD v4.1 (AN 1,612,452). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GRID2
Protein: p.Arg280Lys
Coding: c.839G>A
MANE Select: NM_001510
Type: single nucleotide variant
Location: chr4:93216787 (GRCh38)
Gene constraint: LOEUF 0.332 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.07 · 6 PDB
Residue 280: the 'interaction with cbln1 homotrimer' region; a β-strand

Full GRID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRID2 p.Ala654Thr Pathogenic/Likely pathogenic ★★ same condition
GRID2 p.Ala196Glu Uncertain significance ★★ ⚠ same condition
GRID2 p.Ala21Val Uncertain significance ★★ ⚠ same condition
GRID2 p.Ala574Ser Uncertain significance ★★ ⚠ same condition
GRID2 p.Arg229Gln Uncertain significance ★★ ⚠ same condition
GRID2 p.Arg297Gln Uncertain significance ★★ ⚠ same condition
GRID2 p.Arg439Leu Uncertain significance ★★ same condition
GRID2 p.Arg714Gln 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/grid2-p-arg280lys (accessed [today's date]).

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