PRKN p.Pro417=
c.1251C>T · rs189941210 · VCV2963047
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.5 | |
| Overall | ||
| CADD | 3.792 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/60,020 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.00142%
23/1,614,134 alleles · ultra-rare
exomes 13/1,461,824 · genomes 10/152,310 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 6,002 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| African / African-American | 0.00133% | 75,050 |
| European (non-Finnish) | 0.000678% | 147,498 |
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
- PRKN
- Protein
- p.Pro417=
- Coding
- c.1251C>T
- MANE Select
- NM_004562
- dbSNP
- rs189941210
- Type
- single nucleotide variant
- Location
- chr6:161360122 (GRCh38)
- Gene constraint
- LOEUF 1.17 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 79.10 · 21 PDB
- Residue 417
- a β-strand; the 'triad supradomain' region
Similar variants
- PRKN p.Arg275Trp Pathogenic/Likely pathogenic ★★ same type
- PRKN p.Arg33Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- PRKN p.Arg33Ter Pathogenic ★★ same type
- PRKN p.Arg42Pro Pathogenic ★★ same type
- PRKN p.Cys212Tyr Pathogenic ★★ same type
- PRKN p.Cys253Tyr Pathogenic/Likely pathogenic ★★ same type
- PRKN p.Cys268Ter Pathogenic ★★ same type
- PRKN p.Cys441Arg Pathogenic/Likely pathogenic ★★ 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/prkn-p-pro417 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown