Is PRKN p.Pro37= (c.111G>A) pathogenic?

PRKN p.Pro37= (c.111G>A) is classified Benign in PRKN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-25). Common (popmax 10.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive juvenile Parkinson disease 2.

What condition is associated with PRKN p.Pro37= (c.111G>A)?

PRKN p.Pro37= (c.111G>A) is associated with autosomal recessive juvenile Parkinson disease 2 (ClinVar).

How is Young-onset Parkinson disease inherited?

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

PRKN p.Pro37=

Q: How common is PRKN p.Pro37= (c.111G>A) in the general population?

PRKN p.Pro37= (c.111G>A) is common (popmax 10.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.111G>A · rs77795533 · VCV356020

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 10.7%, afr) — too common for a highly-penetrant pathogenic allele

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.1	GERP -4
Overall
CADD	5.672	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.7% African / African-American · 8,002/74,936 alleles

Filtering AF 10.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.4%

Overall 0.594% 9,592/1,613,604 alleles · common exomes 4,902/1,461,440 · genomes 4,690/152,164 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.7%	9
Admixed American	1.02%	98
Remaining individualsnot grpmax-eligible	0.842%	119
Middle Eastern	0.457%	219
European (non-Finnish)	0.0336%	2,980
South Asian	0.0275%	3,642
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
East Asian	0.00223%	44,854
Finnishnot grpmax-eligible	0.00156%	64,018

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.Pro37=
Coding: c.111G>A
MANE Select: NM_004562
dbSNP: rs77795533
Type: single nucleotide variant
Location: chr6:162443370 (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 37: the ubiquitin-like domain; a UniProt-annotated variant site (in park2)

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.Pro37Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro37 (accessed [today's date]).

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