Apart from structural variants (Spiegler et al., 2018a; Pilz et al., 2020) and somatic mosaicism (McDonald et al., 2014), the here identified CCM1 TSS deletion highlights that variants in regulatory regions that are not always analyzed in routine diagnostics may account for part of the missing heritability in CCM disease. The gene discussed is KRIT1; the disease is cerebral cavernous malformation.