Is GRID2 p.Asp473Glu (c.1419T>A) pathogenic?

GRID2 p.Asp473Glu (c.1419T>A) is classified Uncertain significance in GRID2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-18). AlphaMissense: likely pathogenic (0.7788); Ultra-rare (popmax 0.0245%, eas); Associated with Inborn genetic diseases.

What condition is associated with GRID2 p.Asp473Glu (c.1419T>A)?

GRID2 p.Asp473Glu (c.1419T>A) is associated with Inborn genetic diseases, autosomal recessive spinocerebellar ataxia 18 (ClinVar).

How common is GRID2 p.Asp473Glu (c.1419T>A) in the general population?

GRID2 p.Asp473Glu (c.1419T>A) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

What do computational predictors say about GRID2 p.Asp473Glu (c.1419T>A)?

AlphaMissense predicts likely pathogenic (score 0.7788) — an in-silico prediction, not a clinical call.

GRID2 p.Asp473Glu

c.1419T>A · rs377552413 · VCV522090

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7788 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7788	likely pathogenic
REVEL	0.416	indeterminate
SaProt	LLR -9.34	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.89	GERP -4.3, phastCons 0.012
Regional constraint	o/e 0.90	unconstrained · MANE · 548 kb · p 0.0047 · regional, not allelic
Overall
CADD	19.54	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 0.0245% East Asian · 11/44,862 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00192% 31/1,613,184 alleles · ultra-rare exomes 29/1,460,958 · genomes 2/152,226 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,078
Remaining individualsnot grpmax-eligible	0.024%	4,163
South Asian	0.0022%	45,535
European (non-Finnish)	0.000254%	393,086

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.Asp473Glu
Coding: c.1419T>A
MANE Select: NM_001510
dbSNP: rs377552413
Type: single nucleotide variant
Location: chr4:93422842 (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

Also linked: autosomal recessive spinocerebellar ataxia 18

Similar variants

GRID2 p.Ala654Thr Pathogenic/Likely pathogenic ★★ same condition
GRID2 p.Thr649Ala 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.Arg300His 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-asp473glu (accessed [today's date]).

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