Is PRKN p.Gln347= (c.1041G>A) pathogenic?

PRKN p.Gln347= (c.1041G>A) is classified Conflicting classifications of pathogenicity in PRKN (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-12-23). Very rare (popmax 0.00446%, eas); Associated with autosomal recessive juvenile Parkinson disease 2.

What condition is associated with PRKN p.Gln347= (c.1041G>A)?

PRKN p.Gln347= (c.1041G>A) is associated with autosomal recessive juvenile Parkinson disease 2 (ClinVar).

How common is PRKN p.Gln347= (c.1041G>A) in the general population?

PRKN p.Gln347= (c.1041G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

How is Young-onset Parkinson disease inherited?

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

PRKN p.Gln347=

c.1041G>A · rs766121894 · VCV905718

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

autosomal recessive juvenile Parkinson disease 2

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 1.2	GERP -0.15, phastCons 0.24
Overall
CADD	3.357	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,876 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000248% 4/1,614,192 alleles · very rare exomes 4/1,461,876 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,438
Remaining individualsnot grpmax-eligible	0.0032%	31,253

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.Gln347=
Coding: c.1041G>A
MANE Select: NM_004562
dbSNP: rs766121894
Type: single nucleotide variant
Location: chr6:161548896 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.10 · 21 PDB
Residue 347: the 'triad supradomain' region

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

Disease context

autosomal recessive juvenile Parkinson disease 2 — 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

PRKN p.Arg275Trp Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Arg33Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRKN p.Arg42Pro Pathogenic ★★ same condition
PRKN p.Cys212Tyr Pathogenic ★★ same condition
PRKN p.Cys253Tyr Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Cys441Arg Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Gln25Ter Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Gly284Arg 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/prkn-p-gln347 (accessed [today's date]).

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