This study presents an integrated map of structural variants (SVs) in 2,504 human genomes from 26 populations. The authors constructed an integrated set of eight SV classes, including both balanced and unbalanced variants, using short-read DNA sequencing data and statistically phased onto haplotype blocks. They identified numerous gene-intersecting SVs with population stratification and described naturally occurring homozygous gene knockouts, suggesting the dispensability of various human genes. The SVs were enriched on haplotypes identified by genome-wide association studies and exhibited enrichment for expression quantitative trait loci. The study also uncovered significant levels of SV complexity, including genic loci subject to clusters of repeated rearrangements and complex SVs with multiple breakpoints likely formed through individual mutational events. The catalog will enhance future studies on SV demography, functional impact, and disease association.This study presents an integrated map of structural variants (SVs) in 2,504 human genomes from 26 populations. The authors constructed an integrated set of eight SV classes, including both balanced and unbalanced variants, using short-read DNA sequencing data and statistically phased onto haplotype blocks. They identified numerous gene-intersecting SVs with population stratification and described naturally occurring homozygous gene knockouts, suggesting the dispensability of various human genes. The SVs were enriched on haplotypes identified by genome-wide association studies and exhibited enrichment for expression quantitative trait loci. The study also uncovered significant levels of SV complexity, including genic loci subject to clusters of repeated rearrangements and complex SVs with multiple breakpoints likely formed through individual mutational events. The catalog will enhance future studies on SV demography, functional impact, and disease association.