Is GRM1 p.Val643= (c.1929G>A) pathogenic?

GRM1 p.Val643= (c.1929G>A) is classified Likely benign in GRM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). Very rare (popmax 8.47e-05%, nfe).

How common is GRM1 p.Val643= (c.1929G>A) in the general population?

GRM1 p.Val643= (c.1929G>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

GRM1 p.Val643=

c.1929G>A · rs1376477974 · VCV2907476

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 2.1	GERP 1.3, phastCons 1
Overall
CADD	6.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,980 alleles

Overall 6.2e-05% 1/1,614,040 alleles · very rare exomes 1/1,461,846 · genomes 0/152,194 · 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.Val643=
Coding: c.1929G>A
MANE Select: NM_001278064
dbSNP: rs1376477974
Type: single nucleotide variant
Location: chr6:146398968 (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 643: 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-val643 (accessed [today's date]).

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