PRKN p.His265=
c.795C>T · rs942973988 · VCV1596681
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00667%, afr)
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 4.2 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 7.773 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
African / African-American · 5/74,936 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00161%
Overall
0.000496%
8/1,614,034 alleles · very rare
exomes 7/1,461,828 · genomes 1/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00667% | 14,987 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,243 |
| South Asian | 0.0011% | 91,088 |
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.His265=
- Coding
- c.795C>T
- MANE Select
- NM_004562
- dbSNP
- rs942973988
- Type
- single nucleotide variant
- Location
- chr6:161785848 (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 265
- the 'syt11 binding 2' region; an α-helix; the 'triad supradomain' region
Similar variants
- PRKN p.His265Arg Uncertain significance ★ ⚠ same residue
- PRKN p.His265Tyr Uncertain significance ★ ⚠ same residue
- 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
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-his265 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown