POLE p.Arg559=
c.1675C>A · rs753784391 · VCV1371111
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.81 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.57 | gain · loss 0.18 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 18.63 | PHRED · no single calibrated threshold — expert panels disagree |
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
- POLE
- Protein
- p.Arg559=
- Coding
- c.1675C>A
- MANE Select
- NM_006231
- dbSNP
- rs753784391
- Type
- single nucleotide variant
- Location
- chr12:132672638 (GRCh38)
- Gene constraint
- LOEUF 0.75 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.32 · 18 PDB
- Residue 559
- a β-strand
Similar variants
- POLE p.Arg559Gln Uncertain significance ★★ same residue
- POLE p.Arg559Trp Uncertain significance ★★ ⚠ same residue
- POLE p.Arg559Gly Uncertain significance ★ ⚠ same residue
- POLE p.Arg559Pro Uncertain significance ★ ⚠ same residue
- POLE c.1686+32C>G Pathogenic/Likely pathogenic ★★ same type
- POLE c.3276-1G>C Likely pathogenic ★★ same type
- POLE c.5678+1G>T Pathogenic ★★ same type
- POLE p.Gln1763Ter 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/pole-p-arg559 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown