Is GRID2 p.Arg710Trp (c.2128C>T) pathogenic?

GRID2 p.Arg710Trp (c.2128C>T) is classified Uncertain significance in GRID2 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-15). AlphaMissense: ambiguous (0.5337); Very rare (popmax 0.00892%, eas); Associated with autosomal recessive spinocerebellar ataxia 18.

What condition is associated with GRID2 p.Arg710Trp (c.2128C>T)?

GRID2 p.Arg710Trp (c.2128C>T) is associated with autosomal recessive spinocerebellar ataxia 18 (ClinVar).

How common is GRID2 p.Arg710Trp (c.2128C>T) in the general population?

GRID2 p.Arg710Trp (c.2128C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about GRID2 p.Arg710Trp (c.2128C>T)?

AlphaMissense predicts ambiguous (score 0.5337) — an in-silico prediction, not a clinical call.

GRID2 p.Arg710Trp

Q: How is Autosomal recessive cerebellar ataxia-pyramidal signs-nystagmus-oculomotor apraxia syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.2128C>T · rs750331613 · VCV427806

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5337 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

autosomal recessive spinocerebellar ataxia 18

Computational evidence

Protein change
AlphaMissense	0.5337	ambiguous
REVEL	0.263	benign-leaning
SaProt	LLR -9.49	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 0.41	GERP -2.4, phastCons 0.99
Regional constraint	o/e 0.90	unconstrained · MANE · 548 kb · p 0.0047 · regional, not allelic
Overall
CADD	23.8	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 0.00892% East Asian · 4/44,818 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00143% 23/1,612,558 alleles · very rare exomes 20/1,460,512 · genomes 3/152,046 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,204
Admixed American	0.00334%	29,960
Finnishnot grpmax-eligible	0.00312%	32,009
Remaining individualsnot grpmax-eligible	0.0016%	62,434
African / African-American	0.00134%	74,840
South Asian	0.0011%	91,048
European (non-Finnish)	0.00102%	98,243

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.Arg710Trp
Coding: c.2128C>T
MANE Select: NM_001510
dbSNP: rs750331613
Type: single nucleotide variant
Location: chr4:93515346 (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

autosomal recessive spinocerebellar ataxia 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive cerebellar ataxia-pyramidal signs-nystagmus-oculomotor apraxia syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GRID2 p.Thr649Ala Pathogenic/Likely pathogenic ★★ same condition
GRID2 p.Arg300His Uncertain significance ★★ ⚠ same condition
GRID2 p.Arg367His Uncertain significance ★★ ⚠ same condition
GRID2 p.Asp473Glu Uncertain significance ★★ ⚠ same condition
GRID2 p.Gly391Arg Uncertain significance ★★ ⚠ same condition
GRID2 c.735+21G>C Benign ★★ same condition
GRID2 p.Gly417= Benign ★★ same condition
GRID2 p.Arg224Gln Likely pathogenic ★ ⚠ 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-arg710trp (accessed [today's date]).

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