Is GRM7 p.Cys893Phe (c.2678G>T) pathogenic?

GRM7 p.Cys893Phe (c.2678G>T) is classified Uncertain significance in GRM7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). AlphaMissense: ambiguous (0.4338); Absent from gnomAD v4.1.

How common is GRM7 p.Cys893Phe (c.2678G>T) in the general population?

GRM7 p.Cys893Phe (c.2678G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRM7 p.Cys893Phe (c.2678G>T)?

AlphaMissense predicts ambiguous (score 0.4338) — an in-silico prediction, not a clinical call.

GRM7 p.Cys893Phe

c.2678G>T · rs2470248147 · VCV2110094

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4338 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4338	ambiguous
REVEL	0.75	pathogenic-leaning
SaProt	LLR -6.92	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 879 kb · p 1.2e-10 · regional, not allelic
Overall
CADD	32.0	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.Cys893Phe
Coding: c.2678G>T
MANE Select: NM_000844
dbSNP: rs2470248147
Type: single nucleotide variant
Location: chr3:7680275 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 84.48 · 12 PDB
Residue 893: the 'disordered' region; a UniProt-annotated variant site (in nedshba; does not rescue axon outgrowth defects when expressed in a heterologous system); a UniProt-annotated variant site (in nedshba); a UniProt-annotated variant site (in nedshba; uncertain significance)

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-cys893phe (accessed [today's date]).

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