Study of genetic variants in the context of molecular networks has recently gained much attention. However, many of these studies suffer from the lack of functional information about the network rewiring effect of genetic variants. After large-scale homology modeling, plus extracting native structure from PDB database, we performed structure-based prediction about the rewiring effect using our SNP-IN tool, and it covers significantly more variants than experimental characterization. The analysis result confirms the widespread perturbations in human interactome and reveals the network rewiring behavior based on edge-based network robustness concept.