These results revealed a rare homozygous SMPD1 (sphingomyelin phosphodiesterase 1) variant with uncertain significance (c.808G>A; p. Gly270Ser, CAD score: 23.7, ExAC Frequency: % 0.023, ClinVar Accession: RCV000382375.1) in the extremely severely ill ME/CFS patient. Here, SMPD1 is linked to myalgic encephalomeyelitis/chronic fatigue syndrome.