A new analysis framework called Genomiser combines a pathogenicity score to assess Mendelian non-coding variation with other measures — such as predicted regulatory regions, allele frequency or the phenotypic relevance of associated genes — to improve the identification of regulatory variants from whole-genome sequences. Genomiser takes as input a variant call format (VCF) file obtained from whole-genome sequencing, a list of human phenotype ontology (HPO) terms matching the clinical signs and symptoms observed in the individual under investigation, and optional user parameters. Focusing on small (<25 nucleotides) non-coding mutations, the authors report that Genomiser was able to identify the causative regulatory Mendelian mutation as the top candidate in 77% of simulated whole genomes.