Is GRM7 p.Pro589Ser (c.1765C>T) pathogenic?

GRM7 p.Pro589Ser (c.1765C>T) is classified Uncertain significance in GRM7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: ambiguous (0.3487); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GRM7 p.Pro589Ser (c.1765C>T)?

GRM7 p.Pro589Ser (c.1765C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GRM7 p.Pro589Ser (c.1765C>T) in the general population?

GRM7 p.Pro589Ser (c.1765C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRM7 p.Pro589Ser (c.1765C>T)?

AlphaMissense predicts ambiguous (score 0.3487) — an in-silico prediction, not a clinical call.

GRM7 p.Pro589Ser

c.1765C>T · VCV3282901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3487 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3487	ambiguous
REVEL	0.639	indeterminate
SaProt	LLR -10.80	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 879 kb · p 1.2e-10 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GRM7
Protein: p.Pro589Ser
Coding: c.1765C>T
MANE Select: NM_000844
Type: single nucleotide variant
Location: chr3:7578671 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 84.48 · 12 PDB
Residue 589: a UniProt-annotated variant site (in nedshba; does not rescue axon outgrowth defects when expressed in a heterologous system)

Full GRM7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRM7 p.Ala29Thr Uncertain significance ★★ ⚠ same condition
GRM7 p.Arg493His Uncertain significance ★★ ⚠ same condition
GRM7 p.Arg614Cys Uncertain significance ★★ ⚠ same condition
GRM7 p.Arg9His Uncertain significance ★★ ⚠ same condition
GRM7 p.Glu140Gln Uncertain significance ★★ ⚠ same condition
GRM7 p.Glu501Lys Uncertain significance ★★ ⚠ same condition
GRM7 p.Ile295Val Uncertain significance ★★ ⚠ same condition
GRM7 p.Ile820Met Uncertain significance ★★ ⚠ same condition

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/grm7-p-pro589ser (accessed [today's date]).

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