Though C4 genes are highly homologous and are usually excluded from variant calling analysis, Lundtoft et al. performed a focused analysis into C4 CNVs via targeted sequencing and found Scandinavian SLE patients with a low C4A copy number and carrying a common loss-of-function (LoF) variant presenting with lowered plasma C4 levels (Lundtoft et al., 2022). Here, C4A is linked to systemic lupus erythematosus.