There are three different variations of seipin's amino acid sequence:
* a N → S change in position 88, does not affect protein subcellular location. 
* a S → L change in position 90, does not affect the function in lipid storage.
* a A → P change in position 212 that increases localization to nuclear envelope.
All seipin mutations occur within its loop domain. Between some of these, four large deletions can be found which indicate that at least exons 4 and 5 are required for seipin function in humans. In addition, other six mutations have been identified in the loop domain. The majority of these cluster at the single asparagine-linked glycosylation site (NVS) in seipin. The two mutations that cause neuronal seipinopathy, N88S and S90L, are located directly within this site. Apart from suspending the glycosylation process, these mutations engender an aggregation of seipin and, consequently, the initiation of the ER stress response. The seipin protein can also have a modification residue, that can transform the 289’ and 372’ serine into a phosphoserine, an ester of serine and phosphoric acid.
Overexpression of mutated seipin proteins N88S or S90L can also activate autophagy, and substantially altering the sub-cellular distribution of the autophagosome marker GFP-LC3, which leads to a number of large vacuoles appearing in the cytoplasm. The sub-cellular location of GFP-LC3 and mutated seipin proteins highly overlap. Moreover, these seipin proteins can diffuse small lipid droplets to fuse into larger lipid.
Seipin mutations have been associated with congenital generalized lipodystrophy (see below), and mutations in an N-glycosylation motif links seipin to two other disorders, i.e. Silver syndrome and autosomal-dominant distal hereditary motor neuropathy type V.