Parasite-encoded variant surface antigens (VSAs) like the var gene–encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSA_SM) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSA_UM). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSA_UM to in vitro–selected sublines expressing VSA_SM to identify PfEMP1 responsible for the VSA_SM phenotype. Expression of VSA_SM was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria.