PNKP p.Pro136=
c.408G>A · rs770822417 · VCV390657
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
Conditions
2
Inborn genetic diseases
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 0.89 | GERP -0.84 |
| Overall | ||
| CADD | 8.668 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,096 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000539%
Overall
0.00112%
18/1,614,118 alleles · very rare
exomes 17/1,461,884 · genomes 1/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,365 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| European (non-Finnish) | 0.00119% | 84,289 |
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
- PNKP
- Protein
- p.Pro136=
- Coding
- c.408G>A
- MANE Select
- NM_007254
- dbSNP
- rs770822417
- Type
- single nucleotide variant
- Location
- chr19:49865217 (GRCh38)
- Gene constraint
- LOEUF 1.527 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.06 · 2 PDB
- Residue 136
- the 'disordered' region
Similar variants
- PNKP p.Pro136Ala Uncertain significance ★★ ⚠ same residue
- PNKP p.Pro136Arg Uncertain significance ★★ ⚠ same residue
- PNKP p.Pro136Leu Uncertain significance ★★ ⚠ same residue
- PNKP p.Pro136_Met140dup Uncertain significance ★ same residue
- PNKP c.1126+1G>C Pathogenic/Likely pathogenic ★★ same condition
- PNKP c.1188+1G>A Likely pathogenic ★★ same condition
- PNKP c.1386+1G>C Pathogenic/Likely pathogenic ★★ same condition
- PNKP c.636+1G>T Pathogenic/Likely 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/pnkp-p-pro136 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown