Is POLE c.4150delG pathogenic?

POLE c.4150delG is classified Uncertain significance in POLE (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-19). Very rare (popmax 8.48e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with POLE c.4150delG?

POLE c.4150delG is associated with hereditary neoplastic syndrome (ClinVar).

How common is POLE c.4150delG in the general population?

POLE c.4150delG is very rare (popmax 8.48e-05%, nfe) (gnomAD).

POLE c.4150delG

rs2541903634 · VCV1738262

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

hereditary neoplastic syndrome

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 11	GERP 1.7, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,760 alleles

Overall 6.2e-05% 1/1,612,600 alleles · very rare exomes 1/1,460,324 · genomes 0/152,276 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: POLE
Coding: c.4150delG
MANE Select: NM_006231
dbSNP: rs2541903634
Type: Deletion
Location: chr12:132643977 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 18 PDB

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

POLE c.1359+4_1359+74del Uncertain significance ★★ same condition
POLE c.206_211delCCGAGA Uncertain significance ★★ same condition
POLE c.3459+4del Uncertain significance ★★ same condition
POLE p.Ala1288_Leu1295del Uncertain significance ★★ same condition
POLE p.Gln1950_Glu1956del Uncertain significance ★★ same condition
POLE p.Glu1965_Glu1969del Uncertain significance ★★ same condition
POLE p.Glu223_Arg231del Uncertain significance ★★ same condition
POLE p.Leu1915del Uncertain significance ★★ same condition

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-c-4150delg (accessed [today's date]).

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