POLE p.Pro68=
c.204T>G · rs1470560381 · VCV863883
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.79 | donor loss, 35 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.1 | GERP -3 |
| Overall | ||
| CADD | 1.786 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,898 alleles
Overall
6.2e-05%
1/1,613,944 alleles · very rare
exomes 0/1,461,790 · genomes 1/152,154 · 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
- POLE
- Protein
- p.Pro68=
- Coding
- c.204T>G
- MANE Select
- NM_006231
- dbSNP
- rs1470560381
- Type
- single nucleotide variant
- Location
- chr12:132681138 (GRCh38)
- Gene constraint
- LOEUF 0.75 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.32 · 18 PDB
- Residue 68
- a β-strand
Similar variants
- POLE p.Pro68Ala Uncertain significance ★★ ⚠ same residue
- POLE p.Pro68Thr Uncertain significance ★★ ⚠ same residue
- POLE p.Pro68Leu Uncertain significance ★ same residue
- POLE p.Pro68Ser 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-pro68 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown