The NM_000552.5(VWF):c.2384A>G (p.Tyr795Cys) missense variant has a Grpmax filtering allele frequency in gnomAD v4.1 of 2.800e-7 (based on 2/1180036 alleles in the European non-Finnish population), which is lower than the ClinGen VWD VCEP threshold of <0.005 for type 2N (PM2_Supporting). The computational predictor REVEL gives a score of 0.688, which is above the ClinGen VWD VCEP threshold of >0.644 and predicts a damaging effect on VWF function (PP3). At least three compound heterozygous VWD type 2N patients have been reported with this variant; two (PMIDs: 33807613, 15461624; PM3) compound heterozygous with R854Q (classified Pathogenic by the VWD VCEP), and one (PMID: 15213842) compound heterozygous with R1566X (not yet been evaluated by the VWD VCEP). At least 1 patient with this variant displayed excessive mucocutaneous bleeding as well as low FVIII activity (0.13 IU/ml) and decreased VWF:FVIII binding (<1.5%), which is highly specific for VWD type 2N. (PP4_moderate, PMID:15213842). Factor VIII binding assay performed with theY795C recombinant mutant showed severely impaired binding indicating that this variant has a damaging effect on protein function (PMID: 15213842, 15461624; PS3). In summary, this variant meets the criteria to be classified as Pathogenic for von Willebrand disease type 2N. ACMG/AMP criteria applied as specified by the ClinGen von Willebrand disease Variant Curation Expert Panel: PM2_supporting, PP3, PM3, PP4_moderate, PS3.