GRK1 p.Pro43=
c.129G>A · VCV4920692
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0131%, 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 -9.3 | GERP -3.2 |
| Overall | ||
| CADD | 3.584 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0131%
European (non-Finnish) · 155/1,179,758 alleles
Filtering AF
0.0114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0107%
Overall
0.0104%
168/1,612,990 alleles · ultra-rare
exomes 158/1,460,830 · genomes 10/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0131% | 7,611 |
| Finnishnot grpmax-eligible | 0.011% | 9,071 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,611 |
| Admixed American | 0.00167% | 59,944 |
| African / African-American | 0.00133% | 74,910 |
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.Pro43=
- Coding
- c.129G>A
- MANE Select
- NM_002929
- Type
- single nucleotide variant
- Location
- chr13:113667515 (GRCh38)
- Gene constraint
- LOEUF 1.103 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.04 · 1 PDB
- Residue 43
- the 'n-terminal' region
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-pro43 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown