POLE p.Glu767fs
c.2299_2300insCTACG · VCV4721460
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 20 of 49 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 1.9, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- POLE
- Protein
- p.Glu767fs
- Coding
- c.2299_2300insCTACG
- MANE Select
- NM_006231
- Type
- Insertion
- Location
- chr12:132667522 (GRCh38)
- Gene constraint
- LOEUF 0.75 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.32 · 18 PDB
- Residue 767
- an α-helix; a UniProt-annotated variant site (in imagei)
Similar variants
- POLE p.Glu767Lys Uncertain significance ★★ same residue
- POLE p.Glu767= Likely benign ★★ same residue
- POLE p.Glu767Gln Uncertain significance ★ ⚠ same residue
- POLE c.1794+11_1794+12insA Likely benign ★★ same type
- POLE p.Ala1260fs Pathogenic ★ same type
- POLE p.Asp1214fs Pathogenic ★ same type
- POLE p.Glu386fs Pathogenic ★ same type
- POLE p.His1168fs 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-glu767fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown