Low-Angle Normal Faults (LANFs) represent in the central Southern Alps area (N Italy) the main structures along which the Variscan basement is in contact with the Upper Carboniferous-Permian volcanic-sedimentary succession. Tourmalinites frequently occur along LANFs, usually replacing former cataclasites. The mineralogy and chemical composition of tourmalinites point to a metasomatic origin. LANFs, together with high-angle faults, controlled the opening of the Permian Orobic Basin and likely acted as a preferred pathway for hydrothermal fluids that triggered the Boron-metasomatism. Along the Aga-Vedello LANF, tourmalinites appear to have formed after the cessation of fault activity, as no brittle post-metasomatism deformation overprint has been observed. These relationships suggest that the circulation of B-rich fluids occurred after the opening of the Orobic Basin that is broadly constrained to the Early Permian. At the same time, ca. 285–270 Ma, a strong magmatic activity affected all the Southern Alps, ranging in composition from mafic to acidic rocks and from intrusions at deep crustal levels to effusive volcanic products. The Early Permian magmatism was likely the source of the late-stage hydrothermal fluids that formed the tourmalinites. The same fluids could also have played a significant role in the formation of the Uranium ore deposit of the Novazza-Vedello mining district, as the ore bodies in the Vedello valley are concentrated along the basement-cover contact.