Is GRM7 p.Ser196Phe (c.587C>T) pathogenic?

GRM7 p.Ser196Phe (c.587C>T) is classified Uncertain significance in GRM7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-02). AlphaMissense: likely pathogenic (0.961); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GRM7 p.Ser196Phe (c.587C>T)?

GRM7 p.Ser196Phe (c.587C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GRM7 p.Ser196Phe (c.587C>T) in the general population?

GRM7 p.Ser196Phe (c.587C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about GRM7 p.Ser196Phe (c.587C>T)?

AlphaMissense predicts likely pathogenic (score 0.961) — an in-silico prediction, not a clinical call.

GRM7 p.Ser196Phe

c.587C>T · VCV3855955

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.961 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.961	likely pathogenic
REVEL	0.72	pathogenic-leaning
SaProt	LLR -11.35	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 879 kb · p 1.2e-10 · regional, not allelic
Overall
CADD	29.1	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

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,964 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,048 alleles · very rare exomes 2/1,461,746 · genomes 0/152,302 · 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: GRM7
Protein: p.Ser196Phe
Coding: c.587C>T
MANE Select: NM_000844
Type: single nucleotide variant
Location: chr3:7146519 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 84.48 · 12 PDB
Residue 196: a β-strand

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-ser196phe (accessed [today's date]).

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