The significance and the nature of functional differences between variants at SP-A1 and SP-A2 are poorly understood [14, 49, 50] . Variants aa50 (SP-A1) and aa91 (SP-A2) are located in the collagen region. These changes may affect the oligomerization pattern and binding to receptors such as calreticulin/CD91 or the functional activity of the protein. Likewise, the variants aa219 (SP-A1) and aa223 (SP-A2) are located in the CRD, and might directly influence the binding properties to microorganisms or to surface receptors such as SIRPα or TLR4. Residue 9, and frequently residue 19, is located in the signal peptide, and it is not know whether these variants may affect the function of the protein [14, 44] . Alternatively all the missense variants could be in LD with SNPs in regulatory regions that might affect translation and RNA stability [51, 52] .