ANNOVAR is a tool for functional annotation of genetic variants from high-throughput sequencing data. It annotates single nucleotide variants (SNVs) and insertions/deletions, providing information on their functional consequences, cytogenetic bands, functional importance scores, conserved regions, and variants reported in databases such as the 1000 Genomes Project and dbSNP. ANNOVAR can use annotation databases from the UCSC Genome Browser or any GFF3-compliant database. It also includes a 'variants reduction' protocol to identify functionally important variants from large datasets. ANNOVAR can process 4.7 million variants in about 15 minutes on a desktop computer, making it practical for handling hundreds of human genomes daily. It is freely available at http://www.openbioinformatics.org/annovar/. ANNOVAR provides gene-based, region-based, and filter-based annotations. It can identify variants in genes, introns, exons, regulatory regions, and compare variants to databases such as dbSNP and the 1000 Genomes Project. It can also filter variants based on pre-computed scores like SIFT. ANNOVAR is useful for identifying causal genes in Mendelian diseases by filtering out variants unlikely to be causal. It can also identify 'dispensable' genes with high-frequency non-sense mutations, which are unlikely to be causal for rare diseases. ANNOVAR was tested on synthetic data sets to identify causal genes for Mendelian diseases. It successfully identified the causal gene DHODH for Miller syndrome and MYH3 for Freeman–Sheldon syndrome. It can also handle data from non-human genomes, making it a versatile tool for annotating genetic variants from diverse genomes. ANNOVAR is efficient and flexible, allowing users to customize annotations and filter variants based on various criteria. It is an important tool for prioritizing genetic variants and accelerating scientific discoveries from high-throughput sequencing data.ANNOVAR is a tool for functional annotation of genetic variants from high-throughput sequencing data. It annotates single nucleotide variants (SNVs) and insertions/deletions, providing information on their functional consequences, cytogenetic bands, functional importance scores, conserved regions, and variants reported in databases such as the 1000 Genomes Project and dbSNP. ANNOVAR can use annotation databases from the UCSC Genome Browser or any GFF3-compliant database. It also includes a 'variants reduction' protocol to identify functionally important variants from large datasets. ANNOVAR can process 4.7 million variants in about 15 minutes on a desktop computer, making it practical for handling hundreds of human genomes daily. It is freely available at http://www.openbioinformatics.org/annovar/. ANNOVAR provides gene-based, region-based, and filter-based annotations. It can identify variants in genes, introns, exons, regulatory regions, and compare variants to databases such as dbSNP and the 1000 Genomes Project. It can also filter variants based on pre-computed scores like SIFT. ANNOVAR is useful for identifying causal genes in Mendelian diseases by filtering out variants unlikely to be causal. It can also identify 'dispensable' genes with high-frequency non-sense mutations, which are unlikely to be causal for rare diseases. ANNOVAR was tested on synthetic data sets to identify causal genes for Mendelian diseases. It successfully identified the causal gene DHODH for Miller syndrome and MYH3 for Freeman–Sheldon syndrome. It can also handle data from non-human genomes, making it a versatile tool for annotating genetic variants from diverse genomes. ANNOVAR is efficient and flexible, allowing users to customize annotations and filter variants based on various criteria. It is an important tool for prioritizing genetic variants and accelerating scientific discoveries from high-throughput sequencing data.