Is PINK1 p.Pro322= (c.966C>G) pathogenic?

PINK1 p.Pro322= (c.966C>G) is classified Likely benign in PINK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-25). Ultra-rare (popmax 0.0165%, mid); Associated with autosomal recessive early-onset Parkinson disease 6.

What condition is associated with PINK1 p.Pro322= (c.966C>G)?

PINK1 p.Pro322= (c.966C>G) is associated with autosomal recessive early-onset Parkinson disease 6 (ClinVar).

How common is PINK1 p.Pro322= (c.966C>G) in the general population?

PINK1 p.Pro322= (c.966C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Young-onset Parkinson disease inherited?

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

PINK1 p.Pro322=

c.966C>G · rs199678436 · VCV2713011

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

autosomal recessive early-onset Parkinson disease 6

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 0.27	GERP -2.2, phastCons 0.99
Overall
CADD	10.47	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.000868% 14/1,613,742 alleles · ultra-rare exomes 12/1,461,638 · genomes 2/152,104 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
African / African-American	0.012%	8,332
Remaining individualsnot grpmax-eligible	0.0064%	15,624

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: PINK1
Protein: p.Pro322=
Coding: c.966C>G
MANE Select: NM_032409
dbSNP: rs199678436
Type: single nucleotide variant
Location: chr1:20645566 (GRCh38)
Gene constraint: LOEUF 1.314 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.82 · 6 PDB
Residue 322: a β-strand; the protein kinase domain; a UniProt-annotated variant site (in)

Full PINK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive early-onset Parkinson disease 6 — 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

PINK1 c.1252-1G>A Pathogenic/Likely pathogenic ★★ same condition
PINK1 c.960-2A>G Likely pathogenic ★★ same condition
PINK1 p.Arg492Ter Pathogenic ★★ same condition
PINK1 p.Arg501Ter Pathogenic/Likely pathogenic ★★ same condition
PINK1 p.Gln456Ter Pathogenic ★★ same condition
PINK1 p.Leu347Pro Pathogenic ★★ same condition
PINK1 p.Thr313Met Pathogenic/Likely pathogenic ★★ same condition
PINK1 p.Tyr258Ter 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/pink1-p-pro322 (accessed [today's date]).

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