ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.686A>G (p.Asp229Gly)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV004823288 SCV005442791 likely pathogenic Phenylketonuria 2024-09-06 reviewed by expert panel curation The c.686A>G (p.Asp229Gly) variant in PAH has been reported in 1 individual with PAH deficiency, detected with pathogenic variant p.R408W (PMID: 23357515). This variant is absent in population databases. Computational evidence supports a deleterious effect (REVEL=0.922). Functional studies show the p.Asp229Gly mutant had 0% residual activity as compared to WT PAH activity and decreased protein levels (PMID: 31208052). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PS3_supporting, PP4, PM2_supporting, PM3_supporting, PP3_moderate.

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