Is GRM1 p.Arg25= (c.73A>C) pathogenic?

GRM1 p.Arg25= (c.73A>C) is classified Likely benign in GRM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-02). Very rare (popmax 6.2e-05%).

How common is GRM1 p.Arg25= (c.73A>C) in the general population?

GRM1 p.Arg25= (c.73A>C) is very rare (popmax 6.2e-05%) (gnomAD).

GRM1 p.Arg25=

c.73A>C · rs1790637977 · VCV2997066

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

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 2.7	GERP -2.8, phastCons 0.99
Overall
CADD	8.844	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,012 alleles · very rare exomes 1/1,461,876 · genomes 0/152,136 · joint denominator

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.Arg25=
Coding: c.73A>C
MANE Select: NM_001278064
dbSNP: rs1790637977
Type: single nucleotide variant
Location: chr6:146029590 (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

Similar variants

GRM1 p.Arg25Lys Uncertain significance ★ ⚠ same residue
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

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-arg25 (accessed [today's date]).

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