In our study using a large cohort of individuals with suspected MODY (n=2,471) and control cohorts (n=155,501), we show that ultra-rare heterozygous PTVs and damaging missense variants in APPL1 and WFS1 are not enriched within the MODY cohort, whereas NEUROD1 and PDX1 showed enrichment but at a level in line with our low-penetrance control gene RFX6. This evidence concerns the gene APPL1 and MODY.