PNKP p.Leu135Pro
c.404T>C · VCV4862136
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.0458 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0458 | likely benign |
|---|---|---|
| REVEL | 0.024 | moderately benign-leaning |
| SaProt | LLR -2.94 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP -3.1 |
| Regional constraint | o/e 1.28 | unconstrained · MANE · 5,953 bp · p 5.1e-14 · regional, not allelic |
| Overall | ||
| CADD | 0.035 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PNKP
- Protein
- p.Leu135Pro
- Coding
- c.404T>C
- MANE Select
- NM_007254
- Type
- single nucleotide variant
- Location
- chr19:49865221 (GRCh38)
- Gene constraint
- LOEUF 1.527 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.06 · 2 PDB
- Residue 135
- the 'disordered' region
Similar variants
- PNKP p.Leu135= Likely benign ★★ same residue
- PNKP c.865+1G>A Likely pathogenic ★★ same condition
- PNKP p.Gly375Trp Pathogenic ★★ same condition
- PNKP p.Ala255Thr Uncertain significance ★★ ⚠ same condition
- PNKP p.Ala298Val Uncertain significance ★★ ⚠ same condition
- PNKP p.Ala334Val Uncertain significance ★★ ⚠ same condition
- PNKP p.Ala389Ser Uncertain significance ★★ ⚠ same condition
- PNKP p.Ala441Val Uncertain significance ★★ ⚠ 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/pnkp-p-leu135pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown