Is GRM1 p.Asp271= (c.813C>T) pathogenic?

GRM1 p.Asp271= (c.813C>T) is classified Benign/Likely benign in GRM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-01). Rare (popmax 0.1%, eas).

How common is GRM1 p.Asp271= (c.813C>T) in the general population?

GRM1 p.Asp271= (c.813C>T) is rare (popmax 0.1%, eas) (gnomAD).

GRM1 p.Asp271=

c.813C>T · rs201053682 · VCV746805

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.1%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.38	GERP -3.1, phastCons 0.018
Overall
CADD	7.462	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% East Asian · 45/44,872 alleles

Filtering AF 0.077% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0688%

Overall 0.00434% 70/1,614,192 alleles · rare exomes 64/1,461,868 · genomes 6/152,324 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.1%	997
Remaining individualsnot grpmax-eligible	0.0064%	15,627
European (non-Finnish)	0.00178%	56,191

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.Asp271=
Coding: c.813C>T
MANE Select: NM_001278064
dbSNP: rs201053682
Type: single nucleotide variant
Location: chr6:146159460 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.38 · 8 PDB
Residue 271: an α-helix

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

Similar variants

GRM1 c.2661-7309A>T Uncertain significance ★★ same type
GRM1 c.951-6T>A Uncertain significance ★★ same type
GRM1 p.Ala1005Thr Uncertain significance ★★ ⚠ same type
GRM1 p.Ala11Gly Uncertain significance ★★ ⚠ same type
GRM1 p.Ala883Ser Uncertain significance ★★ ⚠ same type
GRM1 p.Ala91Val Uncertain significance ★★ ⚠ same type
GRM1 p.Arg1185Gln Uncertain significance ★★ ⚠ same type
GRM1 p.Arg358Lys Uncertain significance ★★ ⚠ same type

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-asp271 (accessed [today's date]).

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