Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 17.8%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
autosomal recessive juvenile Parkinson disease 2
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 -1.6 | GERP -3.5 |
| Overall | ||
| CADD | 3.819 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
17.8%
African / African-American · 13,334/75,002 alleles
Filtering AF
17.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 17.4%
Overall
0.951%
15,343/1,614,066 alleles · common
exomes 7,636/1,461,816 · genomes 7,707/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 17.8% | 6 |
| Remaining individualsnot grpmax-eligible | 1.3% | 77 |
| Admixed American | 1.11% | 90 |
| Middle Eastern | 0.94% | 106 |
| South Asian | 0.0461% | 2,169 |
| European (non-Finnish) | 0.0364% | 2,744 |
| East Asian | 0.00223% | 44,872 |
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.Leu261=
- Coding
- c.783A>G
- MANE Select
- NM_004562
- dbSNP
- rs9456711
- Type
- single nucleotide variant
- Location
- chr6:161785860 (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 261
- the 'syt11 binding 2' region; an α-helix; the 'triad supradomain' region
Disease context
autosomal recessive juvenile Parkinson disease 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Young-onset Parkinson disease (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adult
- Prevalence
- 1-5 / 10 000 (Europe)
Similar variants
- PRKN p.Arg275Trp Pathogenic/Likely pathogenic ★★ same condition
- PRKN p.Arg33Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- PRKN p.Arg42Pro Pathogenic ★★ same condition
- PRKN p.Cys212Tyr Pathogenic ★★ same condition
- PRKN p.Cys253Tyr Pathogenic/Likely pathogenic ★★ same condition
- PRKN p.Cys441Arg Pathogenic/Likely pathogenic ★★ same condition
- PRKN p.Gln25Ter Pathogenic/Likely pathogenic ★★ same condition
- PRKN p.Gly284Arg Pathogenic ★★ same condition
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-leu261 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown