Is PAH p.Arg13fs (c.36del) pathogenic?

PAH p.Arg13fs (c.36del) is classified Pathogenic in PAH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-15). Very rare (popmax 0.00133%, afr); Associated with phenylketonuria.

What condition is associated with PAH p.Arg13fs (c.36del)?

PAH p.Arg13fs (c.36del) is associated with phenylketonuria (ClinVar).

How common is PAH p.Arg13fs (c.36del) in the general population?

PAH p.Arg13fs (c.36del) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Phenylketonuria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PAH p.Arg13fs

c.36del · rs1878413079 · VCV1396996

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

phenylketonuria

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 0.73	GERP -2.1, phastCons 0.85
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,926 alleles

Overall 0.000657% 1/152,188 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PAH
Protein: p.Arg13fs
Coding: c.36del
MANE Select: NM_000277
dbSNP: rs1878413079
Type: Deletion
Location: chr12:102917095 (GRCh38)
Gene constraint: LOEUF 1.265 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.04 · 21 PDB

Full PAH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

phenylketonuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Phenylketonuria (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy
Prevalence: 1-9 / 100 000 (France)

Similar variants

PAH p.Arg13= Likely benign ★ same residue
PAH c.1200-1delG Likely pathogenic ★★★ same condition
PAH c.1314_1315+4del Pathogenic ★★★ same condition
PAH c.169_171del Likely pathogenic ★★★ same condition
PAH c.442-1377_509+226del Pathogenic ★★★ same condition
PAH c.442-4403_509+883del Pathogenic ★★★ same condition
PAH c.443_509+1del Pathogenic ★★★ same condition
PAH c.510-19_667del 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-arg13fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown