The seismic cycle on a major fault involves long periods of elastic strain and stress accumulation, driven by aseismic ductile deformation at depth, ultimately released by sudden fault slip events. Coseismic slip distributions are generally heterogeneous with most of the energy being released in the rupture of asperities. Since, on the long term, the fault's walls generally do not accumulate any significant permanent deformation, interseismic deformation might be heterogeneous, revealing zones of focused stress buildup. The pattern of current deformation along the Himalayan arc, which is known to produce recurring devastating earthquakes, and where several seismic gaps have long been recognized, might accordingly show significant lateral variations, providing a possible explanation for the uneven microseismic activity along the Himalayan arc. By contrast, the geodetic measurements show a rather uniform pattern of interseismic strain, oriented consistently with long-term geological deformation, as indicated from stretching lineation. We show that the geodetic data and seismicity distribution are reconciled from a model in which microseismicity is interpreted as driven by stress buildup increase in the interseismic period. The uneven seismicity pattern is shown to reflect the impact of the topography on the stress field, indicating low deviatoric stresses (<35 MPa) and a low friction (<0.3) on the Main Himalayan Thrust. Arc-normal thrusting along the Himalayan front and east-west extension in southern Tibet are quantitatively reconciled by the model.