Is GRM7 p.Ile495= (c.1485C>A) pathogenic?

GRM7 p.Ile495= (c.1485C>A) is classified Likely benign in GRM7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-13). Very rare (popmax 0.00127%, nfe).

How common is GRM7 p.Ile495= (c.1485C>A) in the general population?

GRM7 p.Ile495= (c.1485C>A) is very rare (popmax 0.00127%, nfe) (gnomAD).

GRM7 p.Ile495=

c.1485C>A · rs150784421 · VCV2054273

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00127%, 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 -3.5	GERP -3.4
Overall
CADD	3.665	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 15/1,179,810 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000991% 16/1,613,850 alleles · very rare exomes 16/1,461,628 · genomes 0/152,222 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,502
European (non-Finnish)grpmax	0.00127%	78,654

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile495=
Coding: c.1485C>A
MANE Select: NM_000844
dbSNP: rs150784421
Type: single nucleotide variant
Location: chr3:7461692 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 84.48 · 12 PDB
Residue 495: a UniProt-annotated variant site (in); a β-strand

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-ile495 (accessed [today's date]).

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