PAH p.Asp17fs
c.47_48dup · rs62642906 · VCV2682165
ClinGen expert panel — Phenylketonuria VCEP
Pathogenic for phenylketonuria. Applied ACMG criteria (verbatim):
PVS1 PP4_Moderate PM2_Supporting
Curation rationale (ClinGen, verbatim)
The c.47_48dup (p.Asp17LeufsTer22) variant in PAH is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 1/13 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is reported on 3 alleles of patients with phenylketonuria, with BH4 deficiency excluded (PP4_moderate, PMID: 21147011). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive PAH deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen PAH VCEP: PVS1, PP4_moderate, PM2_supporting. (Phenylketonuria VCEP specifications version 1).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 1 of 13 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP 0.97, phastCons 0.59 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.
Variant & gene context
- Gene
- PAH
- Protein
- p.Asp17fs
- Coding
- c.47_48dup
- MANE Select
- NM_000277
- dbSNP
- rs62642906
- Type
- Microsatellite
- Location
- chr12:102917082 (GRCh38)
- Gene constraint
- LOEUF 1.265 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.04 · 21 PDB
Disease context
phenylketonuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Phenylketonuria (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy
- Prevalence
- 1-9 / 100 000 (France)
Similar variants
- PAH p.Asp17Ter Pathogenic ★★★ same residue
- PAH p.Glu183del Likely pathogenic ★★★ same condition
- PAH p.Glu44del Likely pathogenic ★★★ same condition
- PAH p.Glu57_Asn58insTer Pathogenic ★★★ same condition
- PAH p.Ile95del Pathogenic ★★★ same condition
- PAH p.Leu15_Ser16insTer Pathogenic ★★★ same condition
- PAH p.Leu194fs Pathogenic ★★★ same condition
- PAH p.Leu311fs Pathogenic ★★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pah-p-asp17fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown