Is GRID2 p.Trp14Arg (c.40T>A) pathogenic?

GRID2 p.Trp14Arg (c.40T>A) is classified Uncertain significance in GRID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-15). AlphaMissense: ambiguous (0.5103); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GRID2 p.Trp14Arg (c.40T>A)?

GRID2 p.Trp14Arg (c.40T>A) is associated with Inborn genetic diseases (ClinVar).

How common is GRID2 p.Trp14Arg (c.40T>A) in the general population?

GRID2 p.Trp14Arg (c.40T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRID2 p.Trp14Arg (c.40T>A)?

AlphaMissense predicts ambiguous (score 0.5103) — an in-silico prediction, not a clinical call.

GRID2 p.Trp14Arg

c.40T>A · rs1725285029 · VCV2619088

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5103 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5103	ambiguous
REVEL	0.199	benign-leaning
SaProt	LLR -8.60	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 920 kb · p 0.22 · regional, not allelic
Overall
CADD	24.7	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: GRID2
Protein: p.Trp14Arg
Coding: c.40T>A
MANE Select: NM_001510
dbSNP: rs1725285029
Type: single nucleotide variant
Location: chr4:92304696 (GRCh38)
Gene constraint: LOEUF 0.332 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.07 · 6 PDB

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-trp14arg (accessed [today's date]).

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