Is PINK1 p.Pro95= (c.285T>G) pathogenic?

PINK1 p.Pro95= (c.285T>G) is classified Likely benign in PINK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). Ultra-rare (popmax 0.0443%, afr); Associated with autosomal recessive early-onset Parkinson disease 6.

What condition is associated with PINK1 p.Pro95= (c.285T>G)?

PINK1 p.Pro95= (c.285T>G) is associated with autosomal recessive early-onset Parkinson disease 6 (ClinVar).

How common is PINK1 p.Pro95= (c.285T>G) in the general population?

PINK1 p.Pro95= (c.285T>G) is ultra-rare (popmax 0.0443%, afr) (gnomAD).

How is Young-onset Parkinson disease inherited?

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

PINK1 p.Pro95=

c.285T>G · rs1010013404 · VCV3004858

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0443%, afr)

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 -1.4	GERP -3.1
Overall
CADD	10.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0443% African / African-American · 33/74,454 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0283%

Overall 0.00247% 39/1,578,084 alleles · ultra-rare exomes 17/1,425,868 · genomes 22/152,216 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0443%	2,256
East Asian	0.00461%	21,682
Admixed American	0.00361%	27,710
Remaining individualsnot grpmax-eligible	0.00327%	30,616

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.Pro95=
Coding: c.285T>G
MANE Select: NM_032409
dbSNP: rs1010013404
Type: single nucleotide variant
Location: chr1:20633833 (GRCh38)
Gene constraint: LOEUF 1.314 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.82 · 6 PDB

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-pro95 (accessed [today's date]).

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