Is POLE p.Ile238= (c.714C>A) pathogenic?

POLE p.Ile238= (c.714C>A) is classified Likely benign in POLE (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-20). Absent from gnomAD v4.1.

How common is POLE p.Ile238= (c.714C>A) in the general population?

POLE p.Ile238= (c.714C>A) is absent from gnomAD v4.1 (gnomAD).

POLE p.Ile238=

c.714C>A · rs2136020006 · VCV1100907

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -3.2, phastCons 1
Overall
CADD	5.019	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: POLE
Protein: p.Ile238=
Coding: c.714C>A
MANE Select: NM_006231
dbSNP: rs2136020006
Type: single nucleotide variant
Location: chr12:132677584 (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

Similar variants

POLE p.Ile238Leu Uncertain significance ★★ ⚠ same residue
POLE p.Ile238Phe Conflicting classifications of pathogenicity ★ same residue
POLE p.Ile238Thr Uncertain significance ★ ⚠ same residue
POLE p.Ile238Val Uncertain significance ★ ⚠ same residue
POLE p.Ile238fs Pathogenic ★ same residue
POLE c.1686+32C>G Pathogenic/Likely pathogenic ★★ same type
POLE c.3276-1G>C Likely pathogenic ★★ same type
POLE c.5678+1G>T Pathogenic ★★ 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-ile238 (accessed [today's date]).

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