POLE p.Lys884Ter
c.2650A>T · rs2542062750 · VCV2742812
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 23 of 49 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 37.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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.Lys884Ter
- Coding
- c.2650A>T
- MANE Select
- NM_006231
- dbSNP
- rs2542062750
- Type
- single nucleotide variant
- Location
- chr12:132664060 (GRCh38)
- Gene constraint
- LOEUF 0.75 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.32 · 18 PDB
- Residue 884
- a UniProt-annotated variant site (in imagei)
Similar variants
- POLE p.Lys884Arg Uncertain significance ★★ ⚠ same residue
- POLE p.Lys884= Likely benign ★★ 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
- POLE p.Leu424Val Pathogenic ★★ same type
- POLE p.Pro436Ser 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-lys884ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown