Is DNAJC6 p.Arg40Ile (c.119G>T) pathogenic?

DNAJC6 p.Arg40Ile (c.119G>T) is classified Uncertain significance in DNAJC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-08). Very rare (popmax 0.00471%, nfe); Associated with juvenile onset Parkinson disease 19A.

What condition is associated with DNAJC6 p.Arg40Ile (c.119G>T)?

DNAJC6 p.Arg40Ile (c.119G>T) is associated with juvenile onset Parkinson disease 19A (ClinVar).

How common is DNAJC6 p.Arg40Ile (c.119G>T) in the general population?

DNAJC6 p.Arg40Ile (c.119G>T) is very rare (popmax 0.00471%, nfe) (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.Arg40Ile

c.119G>T · rs754115488 · VCV1445553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00471%, nfe)

Conditions

juvenile onset Parkinson disease 19A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.219	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 103 kb · p 3.7e-07 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00471% European (non-Finnish) · 54/1,145,792 alleles

Filtering AF 0.00369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00331%

Overall 0.00355% 55/1,548,024 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00471%	21,218
Remaining individualsnot grpmax-eligible	0.00167%	59,982

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.Arg40Ile
Coding: c.119G>T
MANE Select: NM_001256864
dbSNP: rs754115488
Type: single nucleotide variant
Location: chr1:65309864 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.29
Residue 40: the '3 x 4 aa approximate tandem repeats' 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-arg40ile (accessed [today's date]).

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