The RIFIN multigene family encodes variant surface antigens of Plasmodium falciparum that play key roles in immune evasion, cytoadhesion, and host-parasite interactions. Despite their importance in malaria pathogenesis, RIFINs remain poorly characterised. Here we present a large-scale comparative and structural analysis of RIFIN diversity using 18 reference genomes alongside 934 field isolates including asymptomatic infection and severe disease. Using a combination of sequence clustering, phylogenetic analysis, and protein structure modelling, we reveal that RIFINs segregate into conserved subgroups reproducible in diverse isolates. Notably, one RIFIN variant was highly conserved across all sampled isolates, in contrast with the high diversity of the wider family, suggesting a potential core functional role. Building on this framework, we integrate these subgroup definitions with RNA-seq expression data to explore associations between RIFIN expression patterns and clinical outcomes to identify functionally relevant RIFIN variants which may contribute to disease outcomes. Together, this work provides a comprehensive overview of RIFIN diversity and structure across parasite populations, establishing a foundation for linking sequence variation to molecular function and disease pathology, and contributes to our understanding of variant surface antigen evolution and host adaptation mechanisms in P. falciparum.