Is GRM2 p.Asp123= (c.369C>T) pathogenic?

GRM2 p.Asp123= (c.369C>T) is classified Likely benign in GRM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). Very rare (popmax 0.00464%, nfe).

How common is GRM2 p.Asp123= (c.369C>T) in the general population?

GRM2 p.Asp123= (c.369C>T) is very rare (popmax 0.00464%, nfe) (gnomAD).

GRM2 p.Asp123=

c.369C>T · rs373995891 · VCV747331

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00464%, nfe)

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 -11	GERP -3.9
Overall
CADD	6.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00464% European (non-Finnish) · 54/1,164,286 alleles

Filtering AF 0.00363% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00325%

Overall 0.00351% 56/1,593,770 alleles · very rare exomes 54/1,441,692 · genomes 2/152,078 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00464%	21,561
Remaining individualsnot grpmax-eligible	0.00163%	61,480
South Asian	0.0011%	90,642

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: GRM2
Protein: p.Asp123=
Coding: c.369C>T
MANE Select: NM_000839
dbSNP: rs373995891
Type: single nucleotide variant
Location: chr3:51709352 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.17 · 31 PDB

Full GRM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRM2 p.Asn824= Benign ★★ same type
GRM2 p.Ala127Glu Uncertain significance ★ ⚠ same type
GRM2 p.Ala275Val Uncertain significance ★ same type
GRM2 p.Ala281Val Uncertain significance ★ ⚠ same type
GRM2 p.Ala287Val Uncertain significance ★ ⚠ same type
GRM2 p.Ala363Thr Uncertain significance ★ ⚠ same type
GRM2 p.Ala430Val Uncertain significance ★ same type
GRM2 p.Ala47Val 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/grm2-p-asp123 (accessed [today's date]).

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