The PAH variant c.1066-1G>A (IVS10-1G>A) is a null variant (acceptor site) located in exon number 11 of the PAH gene. Loss of function in the PAH gene is a known mechanism of disease. Fifteen pathogenic null variants in exon 11 of the PAH gene have been reported. This variant is predicted to disrupt the reading frame by skipping exon 11, altering a region that is critical to protein function (27 pathogenic non-nonsense variants in exon 11 have been reported). The mRNA transcript is predicted to undergo NMD. According to TraP in silico splicing prediction, this alteration is probably damaging (TraP score 0.559). HSF (-35.29 variation) and MaxEnt (-276.58 variation) agree that this alteration of the WT acceptor site most probably affects splicing by breaking the splicing site. The PAH variant c.1066-1G>A (IVS10-1G>A) was found in a Chinese patient with classical PKU (Phe levels >20 mg/dl). BH4 deficiency was excluded by analysis of urinary pterins and dihydropteridine reductase activity in erythrocytes (PMID: 26322415). This variant was also reported in another Chinese patient with undetermined PKU/MHP phenotype (PMID: 26503515). This variant is absent from the gnomAD, ExAC, 1000 Genomes, and ESP population databases. In summary, this variant meets the criteria to be classified as pathogenic. PAH-specific ACMG/AMP criteria applied: PM2, PP4_Moderate, and PVS1.