Is GRM1 p.Pro1071= (c.3213T>G) pathogenic?

GRM1 p.Pro1071= (c.3213T>G) is classified Benign in GRM1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Common (popmax 39%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with spinocerebellar ataxia 44.

What condition is associated with GRM1 p.Pro1071= (c.3213T>G)?

GRM1 p.Pro1071= (c.3213T>G) is associated with spinocerebellar ataxia 44, autosomal recessive spinocerebellar ataxia 13 (ClinVar).

How is Spinocerebellar ataxia type 44 inherited?

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

GRM1 p.Pro1071=

Q: How common is GRM1 p.Pro1071= (c.3213T>G) in the general population?

GRM1 p.Pro1071= (c.3213T>G) is common (popmax 39%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3213T>G · rs1047006 · VCV129212

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 39%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

spinocerebellar ataxia 44

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 -12	GERP -3.8
Overall
CADD	0.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 39% European (non-Finnish) · 460,289/1,179,492 alleles

Filtering AF 38.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 38.9%

Overall 35.4% 570,847/1,613,082 alleles · common exomes 527,670/1,460,964 · genomes 43,177/152,118 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	39.7%	3
European (non-Finnish)grpmax	39%	3
Middle Eastern	35.5%	3
Finnishnot grpmax-eligible	34.7%	3
Remaining individualsnot grpmax-eligible	34.5%	3
Amishnot grpmax-eligible	32.9%	3
South Asian	28.8%	3
Admixed American	26.2%	4
African / African-American	10.2%	10
East Asian	7.06%	14

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: GRM1
Protein: p.Pro1071=
Coding: c.3213T>G
MANE Select: NM_001278064
dbSNP: rs1047006
Type: single nucleotide variant
Location: chr6:146434424 (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

spinocerebellar ataxia 44 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive spinocerebellar ataxia 13

For Spinocerebellar ataxia type 44 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

GRM1 p.Pro1071Arg Uncertain significance ★ ⚠ same residue
GRM1 p.Pro1071Ser Uncertain significance ★ ⚠ same residue
GRM1 c.951-6T>A Uncertain significance ★★ same condition
GRM1 p.Arg358Lys Uncertain significance ★★ ⚠ same condition
GRM1 p.Asn389His 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

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-pro1071 (accessed [today's date]).

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