Abstract: Somatic variants and how to find them: One major challenge in studying somatic mosaicism is the low abundance of potentially pathogenic somatic variant(s). Unlike inherited germline variants, which are essentially present in all cells, pathogenic somatic variants only exist in a subset of cells and may be present at very low (< 1%) variant allele frequency (VAF). Despite the low VAF, these somatic variants are disease-relevant and considered pathogenic. In the context of focal brain malformations, which constitute a frequent cause of drug-resistant focal epilepsy, a pathogenic somatic mammalian target of rapamycin (MTOR) variant with a VAF of 0.3% has been described (Baldassari et al., 2019). The identification of pathogenic somatic variants has important implications both clinically and biologically. Clinically, a positive genetic diagnosis can provide diagnostic certainty and inform genetic counseling. A diagnosis can also improve patient care by informing treatment strategies, for example, justifying the use of an mTOR inhibitor such as sirolimus or everolimus. Biologically, identifying pathogenic somatic variants can provide insights into the origin of somatic mosaicism and the biological pathways that are involved in the condition of interest. As a result, somatic variants and the techniques to identify them are an area of interest to clinicians and the scientific community more broadly.