Is PRKN p.Ala92= (c.276G>A) pathogenic?

PRKN p.Ala92= (c.276G>A) is classified Likely benign in PRKN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-30). Rare (popmax 0.115%, mid); Associated with autosomal recessive juvenile Parkinson disease 2.

How common is PRKN p.Ala92= (c.276G>A) in the general population?

PRKN p.Ala92= (c.276G>A) is rare (popmax 0.115%, mid) (gnomAD).

How is Young-onset Parkinson disease inherited?

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

PRKN p.Ala92=

Q: What condition is associated with PRKN p.Ala92= (c.276G>A)?

PRKN p.Ala92= (c.276G>A) is associated with autosomal recessive juvenile Parkinson disease 2, lung cancer, ovarian neoplasm (ClinVar).

c.276G>A · rs200256562 · VCV697532

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

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 -6.5	GERP -2.9
Overall
CADD	0.871	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% Middle Eastern · 7/6,062 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.00669% 108/1,613,692 alleles · rare exomes 98/1,461,600 · genomes 10/152,092 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	866
South Asian	0.0285%	3,503
African / African-American	0.00667%	14,994
European (non-Finnish)	0.00568%	17,612
Remaining individualsnot grpmax-eligible	0.0048%	20,834

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.Ala92=
Coding: c.276G>A
MANE Select: NM_004562
dbSNP: rs200256562
Type: single nucleotide variant
Location: chr6:162262661 (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 92: a UniProt-annotated variant site (in park2); the 'necessary for pink1-dependent localization to mitochondria' region; the 'disordered' 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

Also linked: lung cancer ovarian neoplasm

For Young-onset Parkinson disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PRKN p.Ala92Thr Uncertain significance ★ ⚠ same residue
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

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-ala92 (accessed [today's date]).

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