Is PARK7 c.252+8A>C pathogenic?

PARK7 c.252+8A>C is classified Likely benign in PARK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). Ultra-rare (popmax 0.0205%, amr); Associated with autosomal recessive early-onset Parkinson disease 7.

What condition is associated with PARK7 c.252+8A>C?

PARK7 c.252+8A>C is associated with autosomal recessive early-onset Parkinson disease 7 (ClinVar).

How common is PARK7 c.252+8A>C in the general population?

PARK7 c.252+8A>C is ultra-rare (popmax 0.0205%, amr) (gnomAD).

How is Young-onset Parkinson disease inherited?

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

PARK7 c.252+8A>C

VCV4804330

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0205%, amr)

Conditions

autosomal recessive early-onset Parkinson disease 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
Splice region	donor +8	near-intronic (+8 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Non-coding constraint	Z -5.56	1 kb window · o/e 1.39 · regional · uncalibrated
Overall
CADD	3.157	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0205% Admixed American · 12/58,652 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00917%

Overall 0.00124% 19/1,536,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0205%	4,888
Remaining individualsnot grpmax-eligible	0.00687%	14,545
European (non-Finnish)	0.000267%	373,993

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
Coding: c.252+8A>C
MANE Select: NM_007262
Type: single nucleotide variant
Location: chr1:7969412 (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-c-252-plus-8a-c (accessed [today's date]).

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