Is PRKN p.Asn58= (c.174T>C) pathogenic?

PRKN p.Asn58= (c.174T>C) is classified Conflicting classifications of pathogenicity in PRKN (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-04-05). Very rare (popmax 0.00662%, sas); Associated with autosomal recessive juvenile Parkinson disease 2.

What condition is associated with PRKN p.Asn58= (c.174T>C)?

PRKN p.Asn58= (c.174T>C) is associated with autosomal recessive juvenile Parkinson disease 2 (ClinVar).

How common is PRKN p.Asn58= (c.174T>C) in the general population?

PRKN p.Asn58= (c.174T>C) is very rare (popmax 0.00662%, sas) (gnomAD).

How is Young-onset Parkinson disease inherited?

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

PRKN p.Asn58=

c.174T>C · rs536687809 · VCV701646

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00662%, sas)

Conditions

autosomal recessive juvenile Parkinson disease 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.9	GERP -0.6, phastCons 1
Overall
CADD	13.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00662% South Asian · 6/90,648 alleles

Filtering AF 0.00287% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00196%

Overall 0.000625% 10/1,598,944 alleles · very rare exomes 7/1,449,050 · genomes 3/149,894 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00662%	15,108
East Asian	0.00447%	22,351
Remaining individualsnot grpmax-eligible	0.00322%	31,059

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.Asn58=
Coding: c.174T>C
MANE Select: NM_004562
dbSNP: rs536687809
Type: single nucleotide variant
Location: chr6:162262763 (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 58: the ubiquitin-like domain; an α-helix

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

For Young-onset Parkinson disease (Orphanet):

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

Similar variants

PRKN p.Arg275Trp Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Arg33Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRKN p.Arg42Pro Pathogenic ★★ same condition
PRKN p.Cys212Tyr Pathogenic ★★ same condition
PRKN p.Cys253Tyr Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Cys441Arg Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Gln25Ter Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Gly284Arg 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-asn58 (accessed [today's date]).

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