GRM7 p.Ser874=
c.2622G>A · rs149426913 · VCV2155847
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.016%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.2 | GERP -4 |
| Overall | ||
| CADD | 1.184 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.016%
African / African-American · 12/75,062 alleles
Filtering AF
0.0092%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0072%
Overall
0.00124%
20/1,614,124 alleles · ultra-rare
exomes 14/1,461,826 · genomes 6/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.016% | 6,255 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,628 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,602 |
| Admixed American | 0.00167% | 60,018 |
| South Asian | 0.0011% | 91,086 |
| European (non-Finnish) | 8.47e-05% | 1,179,976 |
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.Ser874=
- Coding
- c.2622G>A
- MANE Select
- NM_000844
- dbSNP
- rs149426913
- Type
- single nucleotide variant
- Location
- chr3:7680219 (GRCh38)
- Gene constraint
- LOEUF 0.549 · pLI 0.37 (gnomAD)
- Structure
- AlphaFold pLDDT 84.48 · 12 PDB
- Residue 874
- 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)
Similar variants
- GRM7 p.Ser874Leu Uncertain significance ★★ ⚠ same residue
- 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
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-ser874 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown