A tool for reliably predicting the impact of variations on protein stability is extremely important for both protein engineering and for understanding the effects of Mendelian and somatic mutations in the genome. Next Generation Sequencing studies are constantly increasing the number of protein sequences. Given the huge disproportion between protein sequences and structures, there is a need for tools suited to annotate the effect of mutations starting from protein sequence without relying on the structure. Here, we describe INPS, a novel approach for annotating the effect of non-synonymous mutations on the protein stability from its sequence. INPS is based on SVM regression and it is trained to predict the thermodynamic free energy change upon single-point variations in protein sequences.