Is PARK7 p.Ser142Phe (c.425C>T) pathogenic?

PARK7 p.Ser142Phe (c.425C>T) is classified Uncertain significance in PARK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely pathogenic (0.8377); Very rare (popmax 0.0022%, sas); Associated with autosomal recessive early-onset Parkinson disease 7.

What condition is associated with PARK7 p.Ser142Phe (c.425C>T)?

PARK7 p.Ser142Phe (c.425C>T) is associated with autosomal recessive early-onset Parkinson disease 7 (ClinVar).

How common is PARK7 p.Ser142Phe (c.425C>T) in the general population?

PARK7 p.Ser142Phe (c.425C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

How is Young-onset Parkinson disease inherited?

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

What do computational predictors say about PARK7 p.Ser142Phe (c.425C>T)?

AlphaMissense predicts likely pathogenic (score 0.8377) — an in-silico prediction, not a clinical call.

PARK7 p.Ser142Phe

c.425C>T · rs1640786376 · VCV874552

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8377 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal recessive early-onset Parkinson disease 7

Computational evidence

Protein change
AlphaMissense	0.8377	likely pathogenic
REVEL	0.587	indeterminate
SaProt	LLR -13.17	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 22 kb · p 0.79 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,080 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,882 alleles · very rare

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: PARK7
Protein: p.Ser142Phe
Coding: c.425C>T
MANE Select: NM_007262
dbSNP: rs1640786376
Type: single nucleotide variant
Location: chr1:7984909 (GRCh38)
Gene constraint: LOEUF 1.025 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 98.43 · 88 PDB

Full PARK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive early-onset Parkinson disease 7 — 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

PARK7 c.*125G>A Uncertain significance ★★ same condition
PARK7 p.Ala104Thr Uncertain significance ★★ ⚠ same condition
PARK7 p.Ala167Gly Uncertain significance ★★ ⚠ same condition
PARK7 p.Ala179Thr Uncertain significance ★★ ⚠ same condition
PARK7 p.Ile168Val Uncertain significance ★★ ⚠ same condition
PARK7 p.Lys132Arg Uncertain significance ★★ ⚠ same condition
PARK7 p.Thr110Ala Uncertain significance ★★ ⚠ same condition
PARK7 p.Thr34Ile Uncertain significance ★★ ⚠ 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/park7-p-ser142phe (accessed [today's date]).

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