GRK1 p.Phe528=
c.1584T>C · VCV4920784
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0205%, afr)
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 -4.7 | GERP -4.6 |
| Overall | ||
| CADD | 0.339 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0205%
African / African-American · 15/73,016 alleles
Filtering AF
0.0126%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0102%
Overall
0.0013%
20/1,536,920 alleles · ultra-rare
exomes 7/1,384,762 · genomes 13/152,158 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0205% | 4,868 |
| Admixed American | 0.00392% | 25,488 |
| Remaining individualsnot grpmax-eligible | 0.00333% | 30,000 |
| South Asian | 0.00119% | 84,066 |
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.Phe528=
- Coding
- c.1584T>C
- MANE Select
- NM_002929
- Type
- single nucleotide variant
- Location
- chr13:113735255 (GRCh38)
- Gene constraint
- LOEUF 1.103 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.04 · 1 PDB
- Residue 528
- the 'c-terminal' region
Similar variants
- GRK1 p.Phe528Ser Uncertain significance ★ ⚠ same residue
- 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
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-phe528 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown