Is POLE p.Ser752del (c.2255_2257del) pathogenic?

POLE p.Ser752del (c.22552257del) is classified Uncertain significance in POLE (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-18). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with POLE p.Ser752del (c.2255_2257del)?

POLE p.Ser752del (c.2255_2257del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is POLE p.Ser752del (c.2255_2257del) in the general population?

POLE p.Ser752del (c.2255_2257del) is no gnomAD frequency available for this variant (gnomAD).

POLE p.Ser752del

c.2255_2257del · rs878854850 · VCV240430

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 1.9, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: POLE
Protein: p.Ser752del
Coding: c.2255_2257del
MANE Select: NM_006231
dbSNP: rs878854850
Type: Deletion
Location: chr12:132667565 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 18 PDB
Residue 752: a UniProt-annotated variant site (in imagei)

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 p.Ser752= Likely benign ★★ same residue
POLE p.Ser752Ala Uncertain significance ★ ⚠ same residue
POLE p.Ser752Cys Uncertain significance ★ same residue
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

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-ser752del (accessed [today's date]).

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