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The influence of the variability of the soil profile on the translational and rotational kinematic interaction factors of pile foundations is analysed. Variable-withdepth profiles representative of different soil types are considered, and their results are compared to the ones of equivalent homogeneous soils presenting the same average shear wave velocity. The seismic response of the foundation is computed through an efficient numerical model based on the integral reciprocity theorem in elastodynamics and specific Green's functions for the layered half space. The assumption of the variable soil profile generally leads to a higher filtering effect of the soil lateral displacements, and increases the rotation of the foundation. The importance of the soil variability on the response of the supported structure is also analysed in terms of its pseudo-spectral accelerations. The homogeneous assumption is found to be conservative for structures with low periods, while for other systems, specially the ones with an important contribution of the foundation rotation to the structural response, significantly higher maximum accelerations are obtained when considering the variable profile.