Is PINK1 p.Pro142= (c.426G>A) pathogenic?

PINK1 p.Pro142= (c.426G>A) is classified Likely benign in PINK1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-11-01). Ultra-rare (popmax 0.033%, mid); Associated with autosomal recessive early-onset Parkinson disease 6.

What condition is associated with PINK1 p.Pro142= (c.426G>A)?

PINK1 p.Pro142= (c.426G>A) is associated with autosomal recessive early-onset Parkinson disease 6 (ClinVar).

How common is PINK1 p.Pro142= (c.426G>A) in the general population?

PINK1 p.Pro142= (c.426G>A) is ultra-rare (popmax 0.033%, 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.Pro142=

c.426G>A · rs151146709 · VCV1110165

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.1	GERP -4.5
Overall
CADD	0.213	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,056 alleles

Filtering AF 0.00672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00624%

Overall 0.007% 113/1,614,176 alleles · ultra-rare exomes 100/1,461,884 · genomes 13/152,292 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,028
Admixed American	0.01%	10,004
European (non-Finnish)	0.00805%	12,421
Remaining individualsnot grpmax-eligible	0.0064%	15,628
African / African-American	0.004%	25,016
Finnishnot grpmax-eligible	0.00312%	32,018
South Asian	0.0011%	91,082

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.Pro142=
Coding: c.426G>A
MANE Select: NM_032409
dbSNP: rs151146709
Type: single nucleotide variant
Location: chr1:20637880 (GRCh38)
Gene constraint: LOEUF 1.314 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.82 · 6 PDB
Residue 142: an α-helix

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 p.Pro142Leu Uncertain significance ★★ ⚠ same residue
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

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-pro142 (accessed [today's date]).

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