GRID2 p.Asn139=
c.417T>C · rs376999260 · VCV746116
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0583%, amr)
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 -1.9 | GERP -3.5 |
| Overall | ||
| CADD | 4.966 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0583%
Admixed American · 35/60,014 alleles
Filtering AF
0.0431%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0378%
Overall
0.00353%
57/1,614,052 alleles · ultra-rare
exomes 38/1,461,748 · genomes 19/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0583% | 1,715 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| African / African-American | 0.00266% | 37,528 |
| European (non-Finnish) | 0.00144% | 69,411 |
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.Asn139=
- Coding
- c.417T>C
- MANE Select
- NM_001510
- dbSNP
- rs376999260
- Type
- single nucleotide variant
- Location
- chr4:93085167 (GRCh38)
- Gene constraint
- LOEUF 0.332 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.07 · 6 PDB
- Residue 139
- 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-asn139 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown