Is PRKN p.Pro137Ala (c.409C>G) pathogenic?

PRKN p.Pro137Ala (c.409C>G) is classified Uncertain significance in PRKN (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-26). AlphaMissense: likely benign (0.0596); Absent from gnomAD v4.1.

How common is PRKN p.Pro137Ala (c.409C>G) in the general population?

PRKN p.Pro137Ala (c.409C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRKN p.Pro137Ala (c.409C>G)?

AlphaMissense predicts likely benign (score 0.0596) — an in-silico prediction, not a clinical call.

PRKN p.Pro137Ala

c.409C>G · rs1779933576 · VCV1308148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0596 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0596	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -6.07	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 0.87	GERP -2.8, phastCons 0.23
Regional constraint	o/e 1.10	unconstrained · MANE · 1,378 kb · p 0.013 · regional, not allelic
Overall
CADD	1.642	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRKN
Protein: p.Pro137Ala
Coding: c.409C>G
MANE Select: NM_004562
dbSNP: rs1779933576
Type: single nucleotide variant
Location: chr6:162262528 (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 137: the 'necessary for pink1-dependent localization to mitochondria' region

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

Similar variants

PRKN p.Arg275Trp Pathogenic/Likely pathogenic ★★ same type
PRKN p.Arg33Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
PRKN p.Arg33Ter Pathogenic ★★ same type
PRKN p.Arg42Pro Pathogenic ★★ same type
PRKN p.Cys212Tyr Pathogenic ★★ same type
PRKN p.Cys253Tyr Pathogenic/Likely pathogenic ★★ same type
PRKN p.Cys268Ter Pathogenic ★★ same type
PRKN p.Cys441Arg 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-pro137ala (accessed [today's date]).

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