Is GRID2 p.Asp917fs (c.2750del) pathogenic?

GRID2 p.Asp917fs (c.2750del) is classified Uncertain significance in GRID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-27). Rare (popmax 0.601%, sas); Associated with autosomal recessive spinocerebellar ataxia 18.

What condition is associated with GRID2 p.Asp917fs (c.2750del)?

GRID2 p.Asp917fs (c.2750del) is associated with autosomal recessive spinocerebellar ataxia 18 (ClinVar).

How common is GRID2 p.Asp917fs (c.2750del) in the general population?

GRID2 p.Asp917fs (c.2750del) is rare (popmax 0.601%, sas) (gnomAD).

GRID2 p.Asp917fs

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.2750del · VCV4279534

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.601%, sas)

Conditions

autosomal recessive spinocerebellar ataxia 18

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.601% South Asian · 29/4,826 alleles

Filtering AF 0.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.372%

Overall 0.0203% 31/152,342 alleles · rare exomes 0/34 · genomes 31/152,308 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.601%	166
European (non-Finnish)	0.00294%	34,035

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.Asp917fs
Coding: c.2750del
MANE Select: NM_001510 · reported on NM_001440459
Type: Deletion
Location: chr4:93806863 (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 c.1246-278_2193+35240del Uncertain significance ★ same condition
GRID2 c.790-271_1245+268del Uncertain significance ★ same condition
GRID2 c.530-12057_735+24661del36924 Pathogenic same condition
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

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-asp917fs (accessed [today's date]).

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