Genomic inversions occur when a stretch of DNA flips over, reversing its orientation. The absence of copy-number change can make these variants hard to spot. In this commentary, Pagnamenta and colleagues examine an inversion recently reported by Janot et al. in a gene linked to disorders of sexual development. They show it can be detected by genome sequencing, or indirectly via a nearby tagging variant when structural-variant calling is limited, and that it is carried by about 1 in 70,000 people in the UK. By measuring how much identical DNA still borders the inverted segment, they estimate its origin at roughly 2,000 years ago, likely representing an African founder mutation. (By Dr. Alistair T Pagnamenta https://jmg.bmj.com/content/early/2025/12/17/jmg-2025-111258 )