This study presents a comprehensive analysis of the EXO5 gene, which encodes a DNA exonuclease involved in DNArepair that was previously associated with cancer susceptibility.We employed an integrated approach combining genomic and clinicaldata analysis, deep learning variant effect prediction, and moleculardynamics (MD) simulations to investigate the effects of common EXO5 haplotypes on protein structure, dynamics, and canceroutcomes. Here, EXO5 is linked to cancer.