The article introduces ANNOVAR, a tool designed to annotate single nucleotide variants (SNVs) and insertions/deletions (indels) from high-throughput sequencing data. ANNOVAR can identify functionally important variants by examining their impact on genes, inferring cytogenetic bands, reporting functional importance scores, finding variants in conserved regions, and identifying variants reported in public databases like the 1000 Genomes Project and dbSNP. It supports various annotation databases from the UCSC Genome Browser or any GFF3-compliant dataset. The tool is efficient, requiring only about 4 minutes for gene-based annotation and 15 minutes for variant reduction on 4.7 million variants. ANNOVAR is freely available and can be used to prioritize genetic variants for further analysis, particularly in the context of rare Mendelian diseases. The authors demonstrate its utility through a case study on Miller syndrome, where they successfully identified the causal gene DHODH from a large set of variants.The article introduces ANNOVAR, a tool designed to annotate single nucleotide variants (SNVs) and insertions/deletions (indels) from high-throughput sequencing data. ANNOVAR can identify functionally important variants by examining their impact on genes, inferring cytogenetic bands, reporting functional importance scores, finding variants in conserved regions, and identifying variants reported in public databases like the 1000 Genomes Project and dbSNP. It supports various annotation databases from the UCSC Genome Browser or any GFF3-compliant dataset. The tool is efficient, requiring only about 4 minutes for gene-based annotation and 15 minutes for variant reduction on 4.7 million variants. ANNOVAR is freely available and can be used to prioritize genetic variants for further analysis, particularly in the context of rare Mendelian diseases. The authors demonstrate its utility through a case study on Miller syndrome, where they successfully identified the causal gene DHODH from a large set of variants.