Details and references regarding all 230 G6PD protein variants with known mutation are given in supplemental Table 2.

According to a classification proposed in 1971⁸⁷  and universally used since, class IV variants have normal activity; class III variants have enzyme deficiency with residual activity 10% to 60%; class II variants have enzyme deficiency with residual activity <10%; class I variants are those that cause CNSHA. We prefer to consider class II and class III variants as 1 group³⁸  because their clinical manifestations are the same: even though, when they occur, they tend to be more severe, on average and with wide overlap, with class II variants than with class III variants. In view of this, the WHO is currently considering a revision of this classification.

There is 1 example of 2 different mutations resulting in the same amino acid change (F173L); there is 1 example of 2 contiguous base replacements within the same codon (G6PD Palermo); in 2 variants, 2 mutations occur in the same codon; in 1 case, this is the only mutation; in another case, it is associated with another 2 mutations in the nearby codons (G6PD Crispim). Two variants (G6PD Tokyo Glu416Lys, G6PD Herlev Arg198Ser) are reported as class I/II.

Until recently, the only class IV variant was G6PD A (originally characterized because electrophoretically fast compared with the “wild-type” G6PD B). Interestingly, 4 additional class IV variants have been recently discovered in a normal subjects database⁸¹ ).

Two variants with 3-aa replacements

One variant with 3-aa replacements

Fifteen variants with 2 and 3 variants with 3-aa replacements. Only 8 of the variants with multiple amino acid replacements carry an amino acid replacement not found as a single amino acid replacement: these specific amino acid replacements are 11.

Two variants with splicing site mutation and 1 with a nonsense mutation.