Is PAH p.Lys115del (c.339GAA[1]) pathogenic?

PAH p.Lys115del (c.339GAA[1]) is classified Uncertain significance in PAH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-07-20). Very rare (popmax 0.00017%, nfe); Associated with phenylketonuria.

What condition is associated with PAH p.Lys115del (c.339GAA[1])?

PAH p.Lys115del (c.339GAA[1]) is associated with phenylketonuria (ClinVar).

How common is PAH p.Lys115del (c.339GAA[1]) in the general population?

PAH p.Lys115del (c.339GAA[1]) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Phenylketonuria inherited?

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

PAH p.Lys115del

c.339GAA[1] · rs1555207969 · VCV552818

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

phenylketonuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.013	GERP 1.1, phastCons 0.91

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,854 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,012 alleles · very rare exomes 2/1,461,650 · genomes 0/152,362 · joint denominator

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.Lys115del
Coding: c.339GAA[1]
MANE Select: NM_000277
dbSNP: rs1555207969
Type: Microsatellite
Location: chr12:102894743 (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.Lys115fs Pathogenic ★★★ same residue
PAH p.Asp17fs Pathogenic ★★★ same condition
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

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-lys115del (accessed [today's date]).

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