Is DNAJC6 p.Arg48= (c.144G>T) pathogenic?

DNAJC6 p.Arg48= (c.144G>T) is classified Likely benign in DNAJC6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-06). Ultra-rare (popmax 0.0705%, sas); Associated with juvenile onset Parkinson disease 19A.

What condition is associated with DNAJC6 p.Arg48= (c.144G>T)?

DNAJC6 p.Arg48= (c.144G>T) is associated with juvenile onset Parkinson disease 19A (ClinVar).

How common is DNAJC6 p.Arg48= (c.144G>T) in the general population?

DNAJC6 p.Arg48= (c.144G>T) is ultra-rare (popmax 0.0705%, sas) (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.Arg48=

c.144G>T · rs779540362 · VCV1669121

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0705%, sas)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -2.2, phastCons 1
Overall
CADD	12.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0705% South Asian · 59/83,744 alleles

Filtering AF 0.056% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0508%

Overall 0.0092% 142/1,543,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0705%	1,419
Admixed American	0.0612%	1,633
Remaining individualsnot grpmax-eligible	0.0201%	4,983
Middle Eastern	0.0169%	5,918
East Asian	0.00498%	20,097
Ashkenazi Jewishnot grpmax-eligible	0.00353%	28,298
European (non-Finnish)	0.00315%	31,770

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.Arg48=
Coding: c.144G>T
MANE Select: NM_001256864
dbSNP: rs779540362
Type: single nucleotide variant
Location: chr1:65309889 (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.Arg48Pro 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-arg48 (accessed [today's date]).

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