Four cases had the rare variant STXBP2 p.T166M, and the frequency of this variant in the HLH cohort did not differ with that in normal East Asian population [4/224 [1.8%] vs. 5/660 [0.75%], OR 2.382, 95% CI 0.6338–8.951, p = 0.2422], and in silico prediction showed that this variant was benign to the function of the protein, suggesting this variant may not carry pathological significance in HLH. Here, STXBP2 is linked to hemophagocytic syndrome.