GRIN2D p.Pro727=
c.2181C>T · rs773803571 · VCV1580197
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0287%, nfe)
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 -4.6 | GERP -5 |
| Overall | ||
| CADD | 9.604 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0287%
European (non-Finnish) · 339/1,180,020 alleles
Filtering AF
0.0262%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0252%
Overall
0.022%
355/1,614,022 alleles · ultra-rare
exomes 344/1,461,864 · genomes 11/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0287% | 3,481 |
| African / African-American | 0.00801% | 12,485 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| South Asian | 0.00439% | 22,771 |
| Admixed American | 0.00333% | 30,001 |
| East Asian | 0.00223% | 44,882 |
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
- GRIN2D
- Protein
- p.Pro727=
- Coding
- c.2181C>T
- MANE Select
- NM_000836
- dbSNP
- rs773803571
- Type
- single nucleotide variant
- Location
- chr19:48421874 (GRCh38)
- Gene constraint
- LOEUF 0.642 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.00 · 13 PDB
- Residue 727
- an α-helix
Similar variants
- GRIN2D p.Met681Val Pathogenic/Likely pathogenic ★★ same type
- GRIN2D p.Val667Ile Pathogenic/Likely pathogenic ★★ same type
- GRIN2D p.Ala1032Val Uncertain significance ★★ ⚠ same type
- GRIN2D p.Ala1040Thr Uncertain significance ★★ ⚠ same type
- GRIN2D p.Ala1085Thr Uncertain significance ★★ ⚠ same type
- GRIN2D p.Ala1135Thr Uncertain significance ★★ ⚠ same type
- GRIN2D p.Ala1177Thr Uncertain significance ★★ ⚠ same type
- GRIN2D p.Ala1208Val 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/grin2d-p-pro727 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown