GRID2 p.Leu993=
c.2977C>T · rs551908174 · VCV723399
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.12%, eas)
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 4 | GERP 0.75, phastCons 1 |
| Overall | ||
| CADD | 7.718 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.12%
East Asian · 54/44,844 alleles
Filtering AF
0.0947%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0855%
Overall
0.0036%
58/1,611,232 alleles · rare
exomes 48/1,459,006 · genomes 10/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.12% | 830 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,793 |
| Admixed American | 0.00167% | 59,868 |
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
- GRID2
- Protein
- p.Leu993=
- Coding
- c.2977C>T
- MANE Select
- NM_001510
- dbSNP
- rs551908174
- Type
- single nucleotide variant
- Location
- chr4:93772451 (GRCh38)
- Gene constraint
- LOEUF 0.332 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.07 · 6 PDB
Similar variants
- GRID2 p.Ala654Thr Pathogenic/Likely pathogenic ★★ same type
- GRID2 p.Thr649Ala Pathogenic/Likely pathogenic ★★ same type
- GRID2 p.Ala196Glu Uncertain significance ★★ ⚠ same type
- GRID2 p.Ala21Val Uncertain significance ★★ ⚠ same type
- GRID2 p.Ala574Ser Uncertain significance ★★ ⚠ same type
- GRID2 p.Arg229Gln Uncertain significance ★★ ⚠ same type
- GRID2 p.Arg297Gln Uncertain significance ★★ ⚠ same type
- GRID2 p.Arg300His 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/grid2-p-leu993 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown