GRID2 p.Leu144=
c.432C>G · VCV4754023
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0406%, sas)
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 -0.38 | GERP -3.2, phastCons 0.12 |
| Overall | ||
| CADD | 5.239 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0406%
South Asian · 37/91,076 alleles
Filtering AF
0.0303%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0267%
Overall
0.00607%
98/1,613,984 alleles · ultra-rare
exomes 82/1,461,662 · genomes 16/152,322 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0406% | 2,462 |
| Remaining individualsnot grpmax-eligible | 0.0304% | 3,290 |
| African / African-American | 0.0227% | 4,415 |
| East Asian | 0.0111% | 8,974 |
| European (non-Finnish) | 0.0017% | 58,996 |
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.Leu144=
- Coding
- c.432C>G
- MANE Select
- NM_001510
- Type
- single nucleotide variant
- Location
- chr4:93085182 (GRCh38)
- Gene constraint
- LOEUF 0.332 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.07 · 6 PDB
- Residue 144
- the 'interaction with cbln1 homotrimer' region; a β-strand
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-leu144 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown