Is POLE p.Phe1907fs (c.5719_5722del) pathogenic?

POLE p.Phe1907fs (c.57195722del) is classified Pathogenic in POLE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-05). Absent from gnomAD.

How common is POLE p.Phe1907fs (c.5719_5722del) in the general population?

POLE p.Phe1907fs (c.5719_5722del) is absent from gnomAD (gnomAD).

POLE p.Phe1907fs

c.5719_5722del · rs2042024442 · VCV1435296

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 42 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Phe1907fs
Coding: c.5719_5722del
MANE Select: NM_006231
dbSNP: rs2042024442
Type: Microsatellite
Location: chr12:132635981 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 18 PDB
Residue 1907: 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.Phe1907= Likely benign ★★ same residue
POLE p.Phe1907Leu Uncertain significance ★ ⚠ same residue
POLE p.Ile170fs Pathogenic ★★ same type
POLE p.Ala1225dup Uncertain significance ★★ same type
POLE p.Ala782del Uncertain significance ★★ same type
POLE p.Asn1843del Uncertain significance ★★ same type
POLE p.Glu1698del Uncertain significance ★★ same type
POLE p.Glu1966_Ala1967insGlu 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-phe1907fs (accessed [today's date]).

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