Metallic ions are essential for stabilizing the nucleic acid structure, and are also involved in the majority of RNA and DNA biological functions. However, at large concentrations metals may play an opposite role by promoting alterations in the genetic code (mutagenicity). To contribute to the understanding of this effect, theoretical tools are used to investigate the influence of the magnesium dication on the guanine–cytosine (GC) base pair structure and stability. To this end, a fully hydrated Mg2+ cation is inserted in two models: an isolated GC base pair, and a more realistic DNA model corresponding to a hydrated double-stranded trimer. Calculations performed with a hybrid ONIOM approach reveal that the Mg2+ cation coordination to the GC base pair alters drastically the natural tautomeric equilibria in DNA by promoting single proton transfer. Nevertheless, the generated rare tautomer will have a limited impact on the total spontaneous mutation due to the low back-reaction barrier allowing a quick return to the canonical form. Additionally, it is demonstrated that the major effects of biological environment arise from the hydration and stacking influence, whereas the impact of phosphate groups is minor.