Proposal for the molecular pathogenesis of the phenotype in type 1 VWD. There is growing evidence that many (most) cases of mild/moderately severe type 1 VWD are due to a combination of genetic variables both within and outside the VWF locus. Some of these sequence variances may involve distinct polymorphic haplotypes within VWF, some may be located adjacent to, but outside of the VWF gene, and additional modifiers may involve other genes involved in VWF biosynthesis, secretion and clearance. SNP, single nucleotide polymorphism.