GRK1 p.Phe505=
c.1515C>T · VCV4920777
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0232%, 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 4.6 | GERP 2.5, phastCons 1 |
| Overall | ||
| CADD | 8.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0232%
African / African-American · 17/73,176 alleles
Filtering AF
0.0147%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.00137%
21/1,537,232 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0232% | 4,304 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 60,028 |
| European (non-Finnish) | 0.000262% | 382,302 |
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.Phe505=
- Coding
- c.1515C>T
- MANE Select
- NM_002929
- Type
- single nucleotide variant
- Location
- chr13:113735186 (GRCh38)
- Gene constraint
- LOEUF 1.103 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.04 · 1 PDB
- Residue 505
- the agc-kinase c-terminal domain; the 'c-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-phe505 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown