PAH p.Arg252=
c.756G>A · rs1320172123 · VCV1619178
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
phenylketonuria
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.43 | GERP -2.6, phastCons 0.065 |
| Overall | ||
| CADD | 6.776 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PAH
- Protein
- p.Arg252=
- Coding
- c.756G>A
- MANE Select
- NM_000277
- dbSNP
- rs1320172123
- Type
- single nucleotide variant
- Location
- chr12:102852901 (GRCh38)
- Gene constraint
- LOEUF 1.265 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.04 · 21 PDB
- Residue 252
- a UniProt-annotated variant site (in pah deficiency; severe); a UniProt-annotated variant site (in pah deficiency; severe; complete loss of activity); an α-helix
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.Arg252Gln Pathogenic ★★★ same residue
- PAH p.Arg252Gly Pathogenic ★★★ same residue
- PAH p.Arg252Pro Likely pathogenic ★★★ same residue
- PAH p.Arg252Trp Pathogenic ★★★ same residue
- PAH p.Arg252fs Pathogenic ★★★ same residue
- PAH c.1065+1G>A Likely pathogenic ★★★ same condition
- PAH c.1065+1G>T Likely pathogenic ★★★ same condition
- PAH c.1065+3A>G Likely 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-arg252 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown