Is GRM7 p.Ala461Pro (c.1381G>C) pathogenic?

GRM7 p.Ala461Pro (c.1381G>C) is classified Uncertain significance in GRM7 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-30). AlphaMissense: likely pathogenic (0.9504); Absent from gnomAD v4.1.

How common is GRM7 p.Ala461Pro (c.1381G>C) in the general population?

GRM7 p.Ala461Pro (c.1381G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRM7 p.Ala461Pro (c.1381G>C)?

AlphaMissense predicts likely pathogenic (score 0.9504) — an in-silico prediction, not a clinical call.

GRM7 p.Ala461Pro

c.1381G>C · VCV4975907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9504 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9504	likely pathogenic
REVEL	0.789	moderately pathogenic-leaning
SaProt	LLR -13.85	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 879 kb · p 1.2e-10 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Ala461Pro
Coding: c.1381G>C
MANE Select: NM_000844
Type: single nucleotide variant
Location: chr3:7461588 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 84.48 · 12 PDB

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

Similar variants

GRM7 p.Ala29Thr Uncertain significance ★★ ⚠ same type
GRM7 p.Arg493His Uncertain significance ★★ ⚠ same type
GRM7 p.Arg614Cys Uncertain significance ★★ ⚠ same type
GRM7 p.Arg9His Uncertain significance ★★ ⚠ same type
GRM7 p.Asn505Ser Uncertain significance ★★ ⚠ same type
GRM7 p.Cys770Ser Uncertain significance ★★ ⚠ same type
GRM7 p.Glu140Gln Uncertain significance ★★ ⚠ same type
GRM7 p.Glu501Lys 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/grm7-p-ala461pro (accessed [today's date]).

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