Is PRKN p.Arg33Ter (c.97C>T) pathogenic?

PRKN p.Arg33Ter (c.97C>T) is classified Pathogenic in PRKN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-13). Very rare (popmax 0.00167%, amr); Associated with PARK2-related disorders.

What condition is associated with PRKN p.Arg33Ter (c.97C>T)?

PRKN p.Arg33Ter (c.97C>T) is associated with PARK2-related disorders (ClinVar).

How common is PRKN p.Arg33Ter (c.97C>T) in the general population?

PRKN p.Arg33Ter (c.97C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

PRKN p.Arg33Ter

c.97C>T · rs770591350 · VCV853293

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

PARK2-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	50.0	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 0.00167% Admixed American · 1/59,992 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,613,756 alleles · very rare exomes 9/1,461,672 · genomes 1/152,084 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed Americangrpmax	0.00167%	59,992
African / African-American	0.00134%	74,894
European (non-Finnish)	0.000593%	168,575

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg33Ter
Coding: c.97C>T
MANE Select: NM_004562
dbSNP: rs770591350
Type: single nucleotide variant
Location: chr6:162443384 (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 33: the ubiquitin-like domain; an α-helix; a UniProt-annotated variant site (in park2)

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

Disease context

PARK2-related disorders

Similar variants

PRKN p.Arg33Gln Pathogenic/Likely pathogenic ★★ ⚠ same residue
PRKN p.Arg275Trp Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Lys211Asn Pathogenic/Likely pathogenic ★★ same condition
PRKN p.Thr240Met Conflicting classifications of pathogenicity ★ ⚠ same condition
PRKN c.618+7881A>C Likely benign same condition
PRKN p.Arg42Pro Pathogenic ★★ same type
PRKN p.Cys212Tyr Pathogenic ★★ same type
PRKN p.Cys253Tyr Pathogenic/Likely pathogenic ★★ same type

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-arg33ter (accessed [today's date]).

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