Recent genetic sequencing studies in large series’ of predominantly childhood medulloblastoma have implicated loss-of-function, predominantly truncating, variants in theELP1andGPR161genes in causation of the MBSHHsubtype specifically. The latter association, along with a report of an index case with some features of Gorlin syndrome has led to speculation thatGPR161may also cause Gorlin syndrome. We show that these genes are associated with relatively low absolute risks of medulloblastoma from extrapolating lifetime risks in the general population and odds ratios from the population database gnomAD. The projected risks are around 1 in 270–430 forELP1and 1 in 1600–2500 forGPR161.These risks do not suggest the need for MRI screening in infants withELP1orGPR161variants as this is not currently recommended forPTCH1where the risks are equivalent or higher. We also screened 27PTCH1/SUFUpathogenic variant-negative patients with Gorlin syndrome forGPR161and found no suspicious variants. Given the population frequencies of 0.0962% forGPR161and 0.0687% forELP1, neither of these genes can be a cause of Gorlin syndrome with an unexplained population frequency far lower at 0.0021%.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10689-023-00330-7.