PRKN p.Val423=
c.1269A>G · rs1330778122 · VCV2893684
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00424%, nfe)
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 -1.7 | |
| Overall | ||
| CADD | 1.323 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00424%
European (non-Finnish) · 50/1,179,332 alleles
Filtering AF
0.00326%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00294%
Overall
0.0031%
50/1,613,314 alleles · very rare
exomes 49/1,461,126 · genomes 1/152,188 · joint denominator
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.Val423=
- Coding
- c.1269A>G
- MANE Select
- NM_004562
- dbSNP
- rs1330778122
- Type
- single nucleotide variant
- Location
- chr6:161360104 (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 423
- 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-val423 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown