The NM_000277.3:c.545A>G (p.Glu182Gly) variant is a missense variant in exon 6/13 of PAH. The variant was reported in confirmed trans with the p.R261Q allele (Pathogenic per ClinGen PAH VCEP) among two siblings with mild hyperphenylalanemia; BH4 deficiency was not noted to have been formally excluded (PMID: 26542770) (PP1; PM3). The variant has also been previously reported among “two alleles” in a cohort of Armenian PKU patients among whom BH4 deficiency was excluded; no further detail appears to be given (PMID: 10541324) (PP4_Moderate). It has also been noted in ClinVar (ID 102731), without a classification. Three heterozygotes and zero homozygotes for the variant are present in gnomAD, corresponding to a global AF of 0.0000119 and maximum population frequency of 0.0000264 (non-Finnish European population), under the frequency cutoff of 0.0002 for use of PM2 (PM2). The variant is predicted damaging by multiple in-silico missense predictors, including REVEL (REVEL score 0.929) (PP3). Classification: Likely Pathogenic Supporting Criteria: PM2; PM3; PP1; PP4_Moderate; PP3