POLE p.Ala288Val
c.863C>T · VCV3649123
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.2238 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2238 | likely benign |
|---|---|---|
| REVEL | 0.377 | indeterminate |
| SaProt | LLR -11.12 | damaging |
| ⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 0.91 | unconstrained · MANE · 23 kb · p 0.0025 · regional, not allelic |
| Overall | ||
| CADD | 29.2 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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.Ala288Val
- Coding
- c.863C>T
- MANE Select
- NM_006231
- Type
- single nucleotide variant
- Location
- chr12:132676592 (GRCh38)
- Gene constraint
- LOEUF 0.75 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.32 · 18 PDB
- Residue 288
- a turn
Similar variants
- POLE p.Ala288Gly Uncertain significance ★★ ⚠ same residue
- POLE p.Ala288Pro Uncertain significance ★★ ⚠ same residue
- POLE p.Ala288Thr Uncertain significance ★★ ⚠ same residue
- POLE p.Ala288= Benign/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
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-ala288val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown