Is POLE p.Ser752Asn (c.2254_2255delinsAA) pathogenic?

POLE p.Ser752Asn (c.22542255delinsAA) is classified Uncertain significance in POLE (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-07). No gnomAD frequency available for this variant.

How common is POLE p.Ser752Asn (c.2254_2255delinsAA) in the general population?

POLE p.Ser752Asn (c.2254_2255delinsAA) is no gnomAD frequency available for this variant (gnomAD).

POLE p.Ser752Asn

c.2254_2255delinsAA · rs2135970108 · VCV1419579

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 9.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 23 kb · p 0.0025 · regional, not allelic

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.Ser752Asn
Coding: c.2254_2255delinsAA
MANE Select: NM_006231
dbSNP: rs2135970108
Type: Indel
Location: chr12:132667567 (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

Similar variants

POLE p.Ser752del Uncertain significance ★★ same residue
POLE p.Ser752= Likely benign ★★ same residue
POLE p.Ser752Ala Uncertain significance ★ ⚠ same residue
POLE p.Ser752Cys Uncertain significance ★ same residue
POLE p.Ser752Phe Uncertain significance ★ ⚠ same residue
POLE c.6531+4_6531+10delinsAGAAGG Uncertain significance ★★ same type
POLE p.Ala1224Leu Uncertain significance ★★ same type
POLE p.Asp1954Phe Uncertain significance ★★ 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-ser752asn (accessed [today's date]).

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