Is DNAJC6 p.Ser450= (c.1350T>C) pathogenic?

DNAJC6 p.Ser450= (c.1350T>C) is classified Likely benign in DNAJC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). Rare (popmax 0.131%, eas); Associated with juvenile onset Parkinson disease 19A.

What condition is associated with DNAJC6 p.Ser450= (c.1350T>C)?

DNAJC6 p.Ser450= (c.1350T>C) is associated with juvenile onset Parkinson disease 19A (ClinVar).

How common is DNAJC6 p.Ser450= (c.1350T>C) in the general population?

DNAJC6 p.Ser450= (c.1350T>C) is rare (popmax 0.131%, eas) (gnomAD).

How is Atypical juvenile parkinsonism inherited?

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

DNAJC6 p.Ser450=

c.1350T>C · rs202109326 · VCV706557

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.131%, eas)

Conditions

juvenile onset Parkinson disease 19A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.66	GERP 1.7, phastCons 0.033
Overall
CADD	7.571	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.131% East Asian · 59/44,868 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0949%

Overall 0.00427% 69/1,614,152 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.131%	760
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0112%	8,929
Admixed American	0.00167%	60,024
European (non-Finnish)	8.47e-05%	1,180,027

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: DNAJC6
Protein: p.Ser450=
Coding: c.1350T>C
MANE Select: NM_001256864
dbSNP: rs202109326
Type: single nucleotide variant
Location: chr1:65389412 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.29

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.Ser450Ala Uncertain significance ★ ⚠ same residue
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

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-ser450 (accessed [today's date]).

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