Is GRM1 p.Val523= (c.1569G>T) pathogenic?

GRM1 p.Val523= (c.1569G>T) is classified Uncertain significance in GRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-22). Absent from gnomAD v4.1; Associated with autosomal recessive spinocerebellar ataxia 13.

What condition is associated with GRM1 p.Val523= (c.1569G>T)?

GRM1 p.Val523= (c.1569G>T) is associated with autosomal recessive spinocerebellar ataxia 13 (ClinVar).

How common is GRM1 p.Val523= (c.1569G>T) in the general population?

GRM1 p.Val523= (c.1569G>T) is absent from gnomAD v4.1 (gnomAD).

GRM1 p.Val523=

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.1569G>T · VCV3362622

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal recessive spinocerebellar ataxia 13

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	phastCons 1
Overall
CADD	7.669	PHRED · no single calibrated threshold — expert panels disagree

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: GRM1
Protein: p.Val523=
Coding: c.1569G>T
MANE Select: NM_001278064
Type: single nucleotide variant
Location: chr6:146357661 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.38 · 8 PDB

Full GRM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive spinocerebellar ataxia 13 — 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

GRM1 c.951-6T>A Uncertain significance ★★ same condition
GRM1 p.Arg358Lys Uncertain significance ★★ ⚠ same condition
GRM1 p.Leu277Ile Uncertain significance ★★ ⚠ same condition
GRM1 p.Lys276Thr Uncertain significance ★★ ⚠ same condition
GRM1 p.Pro970Leu Uncertain significance ★★ ⚠ same condition
GRM1 p.Ala788= Benign/Likely benign ★★ same condition
GRM1 p.Arg681= Benign/Likely benign ★★ same condition
GRM1 p.Gly1054Asp Benign/Likely benign ★★ 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/grm1-p-val523 (accessed [today's date]).

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