The c.1037G>A variant in PAH is a missense variant predicted to cause substitution of glycine by glutamic acid at amino acid 346 (p.Gly346Glu). At least one patient with this variant displayed plasma phenylalanine concentration persistently above 120umol/L (2mg/dL) AND normal urine pterins and normal DHPR activity excluded a defect of BH4 cofactor metabolism, which is highly specific for PAH deficiency (PP4_Moderate, PMID 19394257). Of reported individuals, one was compound heterozygous for the variant and a pathogenic variant (unknown phase), and one individual was homozygous for the variant (1 point, PMID: 32668217, PM3). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). The computational predictor REVEL gives a score of 0.979, which meets the threshold of 0.932, evidence that correlates with strong impact to PAH function (PP3_Strong). Two missense variants, c.1036G>A (p.Gly346Arg) and c.1036G>C (p.Gly346Arg) [ClinVar Variation ID 102485, 102486], in the same codon have been classified as Likely pathogenic for PAH deficiency by the ClinGen PAH Variant Curation Expert Panel. However, the PAH VCEP is not applying PM5 as evidence since the p.Gly346Glu variant is also classified as Likely pathogenic. In summary, this variant meets the criteria to be classified as Likely pathogenic for autosomal recessive PAH deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen PAH Variant Curation Expert Panel: PP3_strong, PP4_moderate, PM3, PM2_supporting (PAH VCEP specifications version 2.0.0; approved July 16, 2024).