Is POLE p.Phe104fs (c.311del) pathogenic?

POLE p.Phe104fs (c.311del) is classified Pathogenic in POLE (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-19). No gnomAD frequency available for this variant.

How common is POLE p.Phe104fs (c.311del) in the general population?

POLE p.Phe104fs (c.311del) is no gnomAD frequency available for this variant (gnomAD).

POLE p.Phe104fs

c.311del · rs1390420355 · VCV1413890

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 4 of 49
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.5, 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.Phe104fs
Coding: c.311del
MANE Select: NM_006231
dbSNP: rs1390420355
Type: Deletion
Location: chr12:132680197 (GRCh38)
Gene constraint: LOEUF 0.75 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 80.32 · 18 PDB
Residue 104: a β-strand

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

Similar variants

POLE p.Phe104Ser Uncertain significance ★★ ⚠ same residue
POLE c.5379-5_5384del Likely pathogenic ★★ same type
POLE p.Phe48fs Pathogenic/Likely pathogenic ★★ same type
POLE c.1359+4_1359+74del Uncertain significance ★★ same type
POLE c.206_211delCCGAGA Uncertain significance ★★ same type
POLE c.3459+4del Uncertain significance ★★ same type
POLE p.Ala1288_Leu1295del Uncertain significance ★★ same type
POLE p.Gln1950_Glu1956del 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-phe104fs (accessed [today's date]).

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