The rapid development of sequencing technologies has led to the massive growth of genomic variant data, putting in evidence that systematic ways of annotating variants are needed to interpret their impact. For their annotation, the integration of variants into protein functionally annotated sites in 3D has proven in many occasions to be more insightful than just using sequence-based methods alone. However, the gene-to-protein mapping process is very tedious as sometimes there are inconsistencies of data format versions and it requires a certain level of computational resources. Here, we present a pipeline that integrates mutations onto the interfaces of proteins in 3D called “3Dmapper”. By the automatic assignment of mutations to their spatial location we aim for reducing the workload of this task which will positively impact the number of conducted systematic analysis that annotate unidentified putative drivers using 3D structural data. Our workflow can map both previously identified variants and variants of unknown significance. We acknowledge that there are other programs that can be used to map genetic variants to protein three-dimensional structures. However, they present certain limitations when intended to be used with large-scale data. For instance, web based tools are limited to their released database of reference or to a certain number of queries at once or if the stand-alone option is available, you are limited to use a prefixed database. Alternatively, if we would like to use a custom database, then the variants need to be mapped to the entire PDB. This might be time consuming if we only might want to study a subset of proteins. Additionally, no quality parameters are imposed on the protein structure database which may increase the number of false positives results or reduce our mapping ability. Here, we tested 3Dmapper with four sets of human variants (ClinVar, ExAC, TCGA and UK Biobank) to the interface of protein structures. The aim is to update the current protein interfaces coverages as well as testing the correct functioning of the tool.