Is DNAJC6 p.Phe482Leu (c.1446C>A) pathogenic?

DNAJC6 p.Phe482Leu (c.1446C>A) is classified Uncertain significance in DNAJC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely pathogenic (0.9479); Absent from gnomAD v4.1; Associated with juvenile onset Parkinson disease 19A.

What condition is associated with DNAJC6 p.Phe482Leu (c.1446C>A)?

DNAJC6 p.Phe482Leu (c.1446C>A) is associated with juvenile onset Parkinson disease 19A (ClinVar).

How common is DNAJC6 p.Phe482Leu (c.1446C>A) in the general population?

DNAJC6 p.Phe482Leu (c.1446C>A) is absent from gnomAD v4.1 (gnomAD).

How is Atypical juvenile parkinsonism inherited?

Typically Autosomal recessive, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DNAJC6 p.Phe482Leu (c.1446C>A)?

AlphaMissense predicts likely pathogenic (score 0.9479) — an in-silico prediction, not a clinical call.

DNAJC6 p.Phe482Leu

c.1446C>A · rs1645906223 · VCV1409187

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9479 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

juvenile onset Parkinson disease 19A

Computational evidence

Protein change
AlphaMissense	0.9479	likely pathogenic
REVEL	0.688	pathogenic-leaning
SaProt	LLR -4.96	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 5.5, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 103 kb · p 3.7e-07 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F425L vs ClinVar F482L) — verify the residue.

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: DNAJC6
Protein: p.Phe482Leu
Coding: c.1446C>A
MANE Select: NM_001256864
dbSNP: rs1645906223
Type: single nucleotide variant
Location: chr1:65389605 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.29
Residue 482: the 'disordered' region

Full DNAJC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

juvenile onset Parkinson disease 19A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Atypical juvenile parkinsonism (Orphanet):

Inheritance: Autosomal recessive, Not applicable
Onset: Adolescent, Adult

Similar variants

DNAJC6 p.Arg330Ter Pathogenic ★★ same condition
DNAJC6 p.Ala226Val Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Ala234Thr Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Ala277Thr Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Ala611Val Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Ala626Val Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Ala770Val Uncertain significance ★★ ⚠ same condition
DNAJC6 p.Ala836Ser 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/dnajc6-p-phe482leu (accessed [today's date]).

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