Is GRID2 p.Arg439Leu (c.1316G>T) pathogenic?

GRID2 p.Arg439Leu (c.1316G>T) is classified Uncertain significance in GRID2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-31). AlphaMissense: ambiguous (0.4367); Very rare (popmax 0.000351%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GRID2 p.Arg439Leu (c.1316G>T)?

GRID2 p.Arg439Leu (c.1316G>T) is associated with Inborn genetic diseases (ClinVar).

How common is GRID2 p.Arg439Leu (c.1316G>T) in the general population?

GRID2 p.Arg439Leu (c.1316G>T) is very rare (popmax 0.000351%, nfe) (gnomAD).

What do computational predictors say about GRID2 p.Arg439Leu (c.1316G>T)?

AlphaMissense predicts ambiguous (score 0.4367) — an in-silico prediction, not a clinical call.

GRID2 p.Arg439Leu

c.1316G>T · VCV4266881

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4367 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000351%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4367	ambiguous
REVEL	0.376	indeterminate
SaProt	LLR -9.16	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 548 kb · p 0.0047 · regional, not allelic
Overall
CADD	29.8	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 0.000351% European (non-Finnish) · 4/1,139,990 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000255% 4/1,569,586 alleles · very rare exomes 4/1,417,474 · genomes 0/152,112 · joint denominator

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: GRID2
Protein: p.Arg439Leu
Coding: c.1316G>T
MANE Select: NM_001510
Type: single nucleotide variant
Location: chr4:93395677 (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

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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.Arg714Gln Uncertain significance ★★ ⚠ same condition
GRID2 p.Arg966Gly 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-arg439leu (accessed [today's date]).

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