Is PRKN p.Pro113fs (c.337_376del) pathogenic?

PRKN p.Pro113fs (c.337376del) is classified Pathogenic/Likely pathogenic in PRKN (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0325%, nfe); Associated with autosomal recessive juvenile Parkinson disease 2.

What condition is associated with PRKN p.Pro113fs (c.337_376del)?

PRKN p.Pro113fs (c.337_376del) is associated with autosomal recessive juvenile Parkinson disease 2, ovarian cancer, lung cancer (ClinVar).

How common is PRKN p.Pro113fs (c.337_376del) in the general population?

PRKN p.Pro113fs (c.337_376del) is ultra-rare (popmax 0.0325%, nfe) (gnomAD).

How is Young-onset Parkinson disease inherited?

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

PRKN p.Pro113fs

c.337_376del · rs771529549 · VCV846957

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0325%, nfe)

Conditions

autosomal recessive juvenile Parkinson disease 2

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 3 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.7	GERP -2.1
Overall
CADD	34.0	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 0.0325% European (non-Finnish) · 383/1,179,956 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0287%

Overall 0.0257% 415/1,613,842 alleles · ultra-rare exomes 391/1,461,836 · genomes 24/152,006 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0448%	2,232
European (non-Finnish)grpmax	0.0325%	3,081
African / African-American	0.00401%	24,956
Finnishnot grpmax-eligible	0.00156%	63,982

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PRKN
Protein: p.Pro113fs
Coding: c.337_376del
MANE Select: NM_004562
dbSNP: rs771529549
Type: Deletion
Location: chr6:162262561 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.10 · 21 PDB
Residue 113: the 'necessary for pink1-dependent localization to mitochondria' region

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

Disease context

autosomal recessive juvenile Parkinson disease 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ovarian cancer lung cancer

For Young-onset Parkinson disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PRKN c.1083+1del Pathogenic ★★ same condition
PRKN p.Asn52fs Pathogenic ★★ same condition
PRKN p.Gln34fs Pathogenic ★★ same condition
PRKN p.Leu331fs Likely pathogenic ★★ same condition
PRKN c.172-18del Benign/Likely benign ★★ same condition
PRKN c.106_269del Pathogenic ★ same condition
PRKN c.(171+1_172-1 Pathogenic ★ same condition
PRKN c.(171+1_172-12671 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/prkn-p-pro113fs (accessed [today's date]).

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