The absence of severe obesity in some family members carrying PHIP STRICT missense and LOF variants, the absence of developmental delay in some probands with LOF mutations (Table 3), and the presence of STRICT missense variants in control participants without obesity (6/9 controls who were carriers of very rare STRICT variants had a BMI < 30 kg/m2) suggest variable penetrance. This evidence concerns the gene PHIP and obesity due to melanocortin 4 receptor deficiency.