Is PRKN p.Met1Val (c.1A>G) pathogenic?

PRKN p.Met1Val (c.1A>G) is classified Pathogenic/Likely pathogenic in PRKN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-01-02). Very rare (popmax 0.00714%, amr); Associated with young-onset Parkinson disease.

What condition is associated with PRKN p.Met1Val (c.1A>G)?

PRKN p.Met1Val (c.1A>G) is associated with young-onset Parkinson disease (ClinVar).

How common is PRKN p.Met1Val (c.1A>G) in the general population?

PRKN p.Met1Val (c.1A>G) is very rare (popmax 0.00714%, amr) (gnomAD).

How is Young-onset Parkinson disease inherited?

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

PRKN p.Met1Val

c.1A>G · rs772786691 · VCV493448

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00714%, amr)

Conditions

young-onset Parkinson disease

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.837	moderately pathogenic-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00714% Admixed American · 4/55,994 alleles

Filtering AF 0.00237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.000758% 12/1,583,202 alleles · very rare exomes 10/1,431,164 · genomes 2/152,038 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00714%	13,999
Remaining individualsnot grpmax-eligible	0.00163%	61,216
African / African-American	0.00135%	74,108
European (non-Finnish)	0.000515%	194,287

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: PRKN
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_004562
dbSNP: rs772786691
Type: single nucleotide variant
Location: chr6:162727668 (GRCh38)

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

Disease context

young-onset Parkinson disease — 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)

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/prkn-p-met1val (accessed [today's date]).

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