Is GRM1 p.Phe376= (c.1128C>T) pathogenic?

GRM1 p.Phe376= (c.1128C>T) is classified Benign in GRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-22). Rare (popmax 0.169%, sas).

How common is GRM1 p.Phe376= (c.1128C>T) in the general population?

GRM1 p.Phe376= (c.1128C>T) is rare (popmax 0.169%, sas) (gnomAD).

GRM1 p.Phe376=

c.1128C>T · rs563754946 · VCV2154015

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.169%, sas)

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 4.8	GERP 2.1, phastCons 1
Overall
CADD	12.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.169% South Asian · 154/91,076 alleles

Filtering AF 0.147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.139%

Overall 0.0102% 164/1,614,004 alleles · rare exomes 154/1,461,798 · genomes 10/152,206 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.169%	591
Remaining individualsnot grpmax-eligible	0.016%	6,250

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.Phe376=
Coding: c.1128C>T
MANE Select: NM_001278064
dbSNP: rs563754946
Type: single nucleotide variant
Location: chr6:146304788 (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 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-phe376 (accessed [today's date]).

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