This variant has been detected in one individual with PAH deficiency (PMID: 36104584). This individual was a compound heterozygote for the variant and a pathogenic variant, p.Arg408Gln, in trans (phase confirmed by parental testing) (PMID: 36104584). This individual had plasma phenylalanine >120 μmol/L with the exclusion of a defect of BH4 cofactor metabolism (PP4_Moderate) (PMID: 36104584). The highest population minor allele frequency in gnomAD v2.1.1 is 0.001 (20/19766 alleles) in the East Asian population (none of the population data codes are met). The computational splicing predictor SpliceAI gives a score of 0.05 for donor loss suggesting that the variant has no impact on splicing (BP4). There is a ClinVar entry for this variant (Variation ID: 102503, 1 star review status) with one submitter classifying the variant as a variant of uncertain significance, one submitter classifying the variant as likely benign, and one submitter classifying the variant as benign. Due to conflicting evidence, this variant is classified as a variant of unknown significance for PAH deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen PAH Variant Curation Expert Panel (Specifications Version 2.0): PM3, PP4, BP4.