Is POLE p.Pro489_Asp490= (c.1467_1470delinsTGAT) pathogenic?

POLE p.Pro489Asp490= (c.14671470delinsTGAT) is classified Benign in POLE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-11). Associated with colorectal cancer, susceptibility to, 12.

What condition is associated with POLE p.Pro489_Asp490= (c.1467_1470delinsTGAT)?

POLE p.Pro489_Asp490= (c.1467_1470delinsTGAT) is associated with colorectal cancer, susceptibility to, 12 (ClinVar).

POLE p.Pro489_Asp490=

c.1467_1470delinsTGAT · VCV3904119

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

colorectal cancer, susceptibility to, 12

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.82	GERP -1.7

Variant & gene context

Gene: POLE
Protein: p.Pro489_Asp490=
Coding: c.1467_1470delinsTGAT
MANE Select: NM_006231
Type: Indel
Location: chr12:132673167 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 18 PDB
Residue 489: an α-helix

Full POLE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

colorectal cancer, susceptibility to, 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

POLE p.Ala1224Leu Uncertain significance ★★ same condition
POLE p.Glu912Met Uncertain significance ★★ same condition
POLE p.Pro489His Uncertain significance ★★ ⚠ same residue
POLE c.910-18_910-17delinsTT Likely benign ★★ same condition
POLE p.Ala480_Leu481= Benign/Likely benign ★★ same condition
POLE c.423+2_423+4delinsAGT Uncertain significance ★ same condition
POLE p.Pro489Leu Uncertain significance ★ ⚠ same residue
POLE p.Pro489Ser Uncertain significance ★ ⚠ same residue

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-pro489-asp490 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown