In a study of Autoimmune Lymphoproliferative Disease (ALD), 28 patients with Dianzani ALD (DALD) were screened for variants in PRF1. This variant was seen more often in these cases than in the 816 controls: case var/var: 1, case var/wt: 5, case wt/wt: 22, cont var/var: 3, cont var/wt: 69, cont wt/wt: 744. The allele frequency difference between the cases and controls has a significance of p = 0.0165.
According to Orphanet this is a “rare disease” with an incidence of less than 1 in 2000. From this we estimate that if this variant causes an increased susceptibility to this disease, the attributable increased risk is still less than 1%.
DNA from 75 unrelated patients with acquired aplastic anemia were sequenced for PRF1. Of these, three were heterozygous for this A91V variant. The authors report studying >1000 individuals and find an allele frequency of 1%, without much variation between ethnic groups. Their observation of this variant in the patients is not significant — the authors report a p-value of 0.27.
These authors claim an alele frequency of 8-9% (no citation or data given). Investigating the effect of this variant in cytotoxic T lymphocytes found that cells expressing this variant had about half cytotoxicity compared to wild type. The purified proteins, when tested directly on target cells, had a more pronounced reduction in cytotoxic function (>10-fold).