GRIN1 p.Pro557=
c.1671G>A · VCV4710107
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00242%, eas)
Conditions
1
neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant
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 -0.85 | GERP -2.1, phastCons 0.003 |
| Overall | ||
| CADD | 8.858 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00242%
East Asian · 1/41,296 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000259%
4/1,544,422 alleles · very rare
exomes 4/1,392,116 · genomes 0/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00242% | 41,296 |
| South Asian | 0.00119% | 84,304 |
| European (non-Finnish) | 0.000174% | 574,660 |
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
- GRIN1
- Protein
- p.Pro557=
- Coding
- c.1671G>A
- MANE Select
- NM_007327
- Type
- single nucleotide variant
- Location
- chr9:137162210 (GRCh38)
- Structure
- AlphaFold pLDDT 44.02
- Residue 557
- the 'disordered' region
Similar variants
- GRIN1 p.Pro557Leu Likely pathogenic ★★ same residue
- GRIN1 p.Pro557Arg Pathogenic/Likely pathogenic ★★ same residue
- GRIN1 p.Arg659Gln Pathogenic/Likely pathogenic ★★ same condition
- GRIN1 p.Arg659Trp Pathogenic ★★ same condition
- GRIN1 p.Arg794Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- GRIN1 p.Arg844Cys Pathogenic/Likely pathogenic ★★ same condition
- GRIN1 p.Arg844Leu Pathogenic/Likely pathogenic ★★ same condition
- GRIN1 p.Asp227His Likely pathogenic ★★ same condition
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/grin1-p-pro557 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown