POLE p.Phe332fs
c.993dup · VCV4726927
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 10 of 49 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.7, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- POLE
- Protein
- p.Phe332fs
- Coding
- c.993dup
- MANE Select
- NM_006231
- Type
- Duplication
- Location
- chr12:132676120 (GRCh38)
- Gene constraint
- LOEUF 0.75 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.32 · 18 PDB
Similar variants
- POLE p.Phe332= Benign/Likely benign ★★ same residue
- POLE p.Phe332Leu Uncertain significance ★ ⚠ same residue
- POLE c.802-2dup Uncertain significance ★★ same type
- POLE c.802-7_818dup Uncertain significance ★★ same type
- POLE p.Asp1026_Leu1032dup Uncertain significance ★★ same type
- POLE p.Gln1950_Glu1956dup Uncertain significance ★★ same type
- POLE p.Glu1963_Asn1971dup Uncertain significance ★★ same type
- POLE p.Ile1864dup Uncertain significance ★★ 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-phe332fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown