Is PRKN p.Pro73= (c.219G>A) pathogenic?

PRKN p.Pro73= (c.219G>A) is classified Likely benign in PRKN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-02). Very rare (popmax 0.005%, nfe); Associated with ovarian neoplasm.

What condition is associated with PRKN p.Pro73= (c.219G>A)?

PRKN p.Pro73= (c.219G>A) is associated with ovarian neoplasm, lung cancer, autosomal recessive juvenile Parkinson disease 2 (ClinVar).

How common is PRKN p.Pro73= (c.219G>A) in the general population?

PRKN p.Pro73= (c.219G>A) is very rare (popmax 0.005%, nfe) (gnomAD).

PRKN p.Pro73=

c.219G>A · rs139083077 · VCV1130407

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, nfe)

Conditions

ovarian neoplasm

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 -5.3	GERP -2.9
Overall
CADD	4.395	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% European (non-Finnish) · 59/1,179,812 alleles

Filtering AF 0.00394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00361%

Overall 0.00428% 69/1,610,918 alleles · very rare exomes 62/1,460,744 · genomes 7/150,174 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.005%	19,997
African / African-American	0.00405%	24,709
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,590
Admixed American	0.00335%	29,855
Remaining individualsnot grpmax-eligible	0.0032%	31,218
East Asian	0.00223%	44,798
South Asian	0.0011%	91,020

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.Pro73=
Coding: c.219G>A
MANE Select: NM_004562
dbSNP: rs139083077
Type: single nucleotide variant
Location: chr6:162262718 (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 73: the ubiquitin-like domain

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

Disease context

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

Also linked: lung cancer autosomal recessive juvenile Parkinson disease 2

Similar variants

PRKN p.Pro73Leu Uncertain significance ★ ⚠ 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-pro73 (accessed [today's date]).

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