GRK1 p.Pro412=
c.1236C>T · VCV4920761
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.629%, sas)
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 -13 | GERP -2.3 |
| Overall | ||
| CADD | 0.174 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.629%
South Asian · 529/84,050 alleles
Filtering AF
0.585%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.567%
Overall
0.0625%
961/1,536,872 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.629% | 159 |
| East Asian | 0.447% | 224 |
| Remaining individualsnot grpmax-eligible | 0.165% | 606 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0175% | 5,730 |
| Middle Eastern | 0.0167% | 5,990 |
| European (non-Finnish) | 0.0118% | 8,496 |
| Admixed American | 0.00784% | 12,750 |
| African / African-American | 0.00547% | 18,287 |
| Finnishnot grpmax-eligible | 0.00221% | 45,300 |
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
- GRK1
- Protein
- p.Pro412=
- Coding
- c.1236C>T
- MANE Select
- NM_002929
- Type
- single nucleotide variant
- Location
- chr13:113732925 (GRCh38)
- Gene constraint
- LOEUF 1.103 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.04 · 1 PDB
- Residue 412
- the protein kinase domain
Similar variants
- GRK1 c.1194+1G>A Pathogenic/Likely pathogenic ★★ same type
- GRK1 p.Val380Asp Pathogenic/Likely pathogenic ★★ same type
- GRK1 p.Ala18Thr Uncertain significance ★★ ⚠ same type
- GRK1 p.Ala394Val Uncertain significance ★★ ⚠ same type
- GRK1 p.Arg31Trp Uncertain significance ★★ same type
- GRK1 p.Arg51Cys Uncertain significance ★★ ⚠ same type
- GRK1 p.Asp262His Uncertain significance ★★ ⚠ same type
- GRK1 p.Gly144Trp 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/grk1-p-pro412 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown