gnomAD

The Genome Aggregation Database (gnomAD) is a public resource that aggregates and harmonizes human genome and exome sequencing data from diverse projects to provide population-level allele frequencies and variant annotations. It builds on the earlier Exome Aggregation Consortium (ExAC) effort and is maintained by the Broad Institute and collaborators. By combining data from thousands of individuals, gnomAD offers insight into how common or rare specific genetic variants are across populations, helping to avoid misclassification of benign variation as pathogenic.

The dataset includes aggregated variant calls from exome and whole-genome sequencing, with frequencies reported for multiple populations and overall. It provides quality metrics and functional annotations, as well as gene-level constraint metrics such as pLI and LOEUF, which indicate how tolerant a gene is to loss-of-function variation. This combination enables researchers and clinicians to interpret the potential impact of genetic variants more accurately.

gnomAD is widely used in clinical and research genomics to filter common variants during rare-disease interpretation, prioritize rare or potentially damaging variants, and support population genetics studies. Access is provided through a web browser and downloadable data, including summary statistics and VCF files, with accompanying documentation describing processing steps and caveats.

Limitations include underrepresentation of certain populations, differences in sequencing platforms and pipelines across contributing studies, and residual technical artifacts. Users are encouraged to consult the documentation to interpret frequencies and constraints appropriately.