PRKN p.Lys76=
c.228A>G · rs370161857 · VCV1149409
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00458%, nfe)
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 -1.1 | GERP -0.96 |
| Overall | ||
| CADD | 5.525 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00458%
European (non-Finnish) · 54/1,179,856 alleles
Filtering AF
0.00358%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00321%
Overall
0.00354%
57/1,611,938 alleles · very rare
exomes 50/1,460,958 · genomes 7/150,980 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00458% | 21,849 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,227 |
| African / African-American | 0.00134% | 74,502 |
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.Lys76=
- Coding
- c.228A>G
- MANE Select
- NM_004562
- dbSNP
- rs370161857
- Type
- single nucleotide variant
- Location
- chr6:162262709 (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 76
- the ubiquitin-like domain
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-lys76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown