No known publications, found heterozygously in 4 out of 64 PGP + public genomes (allele frequency of 3.1%). Because we are evaluating variants as they are seen in genomes, this is a biased estimate of frequency — a less biased estimate might be 3 out of 63 (allele frequency 2.4%). This is a start codon mutation and therefore predicted to be extremely disruptive through disrupting proper initiation of translation within the ribosome. A different mutation in this gene (Arg248Try) has been reported to cause autoimmune lymphoproliferative syndrome by one group (Chun et al.) but, as far as we know, there are no other publications linking the gene to inherited disease. The same group provided a large amount of functional characterization of the variant supporting the Arg248Try as having a damaging effect.
With an allele frequency of 2.4%, 1 in 1500 to 2000 individuals are predicted to be homozygous. The disease, on the other hand, is expected to be quite rare — this implies that either this variant does not have a significant disruptive effect (possibly due to alternative splicing or an alternative start codon), the disease is severely underdiagnosed (possibly less extreme), or that the hypothesis of Chun et al for this gene as being causal was mistaken. We suspect the first possibility is the case, as there are several other transcripts recorded for this gene, many of which do not include this position as an exon.