The NM_000277.2(PAH):c.1130A>G (p.Tyr377Cys) variant is a missense variant in exon 11/13 of PAH. The variant has been previously reported in trans with p.R243* (Pathogenic in ClinVar and per ClinGen PAH VCEP) in a PKU patient (plasma Phe 765 umol/L); BH4 deficiency was excluded by analysis of urinary pterins and dihydropterine reductase assays (PMID: 22526846) (PM3; PP4_Moderate). One heterozygote and zero homozygotes are present for the variant in gnomAD, corresponding to a global frequency of 0.00000398 and a maximum population frequency (non-Finnish European) of 0.00000879, 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 0.849), so PP3 is met. PM5 also applies because a different missense variant at the same amino acid residue, p.Y377D, qualifies as Likely Pathogenic: the p.Y377D variant has been previously reported in trans with the known pathogenic c.1066-11G>A splicing mutation in a proband with PKU (plasma Phe 20-30mg/dL; BH4 formally excluded by urinary pterin and DHPR analysis) (PMID: 21890392) (PM3; PP4_Moderate), is absent in ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2), and is predicted damaging by multiple in-silico missense predictors, including REVEL (REVEL score 0.874) (PP3). Classification: Likely Pathogenic Supporting Criteria: PM2; PM3; PP4_Moderate; PM5, PP3