Is PRKN p.Arg97Gln (c.290G>A) pathogenic?

PRKN p.Arg97Gln (c.290G>A) is classified Uncertain significance in PRKN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0727); Very rare (popmax 0.00669%, eas); Associated with Inborn genetic diseases.

What condition is associated with PRKN p.Arg97Gln (c.290G>A)?

PRKN p.Arg97Gln (c.290G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PRKN p.Arg97Gln (c.290G>A) in the general population?

PRKN p.Arg97Gln (c.290G>A) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about PRKN p.Arg97Gln (c.290G>A)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

PRKN p.Arg97Gln

c.290G>A · rs369634041 · VCV2417723

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.22	benign-leaning
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.043	GERP -1.3
Regional constraint	o/e 1.10	unconstrained · MANE · 1,378 kb · p 0.013 · regional, not allelic
Overall
CADD	10.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00669% East Asian · 3/44,872 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00204% 33/1,613,758 alleles · very rare exomes 30/1,461,594 · genomes 3/152,164 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,957
Admixed American	0.005%	20,001
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)	0.00212%	47,199
South Asian	0.0011%	91,064

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.Arg97Gln
Coding: c.290G>A
MANE Select: NM_004562
dbSNP: rs369634041
Type: single nucleotide variant
Location: chr6:162262647 (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 97: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRKN p.Ala91Val Uncertain significance ★★ ⚠ same condition
PRKN p.Arg191Gln Uncertain significance ★★ ⚠ same condition
PRKN p.Arg191Trp Uncertain significance ★★ ⚠ same condition
PRKN p.Arg234Trp Uncertain significance ★★ ⚠ same condition
PRKN p.Asp39Glu Uncertain significance ★★ ⚠ same condition
PRKN p.Cys268Ser Uncertain significance ★★ ⚠ same condition
PRKN p.Gly329Cys Uncertain significance ★★ ⚠ same condition
PRKN p.Ile236Val 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/prkn-p-arg97gln (accessed [today's date]).

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