Is DNAJC6 p.Glu500= (c.1500G>A) pathogenic?

DNAJC6 p.Glu500= (c.1500G>A) is classified Benign in DNAJC6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 53.7%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with juvenile onset Parkinson disease 19A.

What condition is associated with DNAJC6 p.Glu500= (c.1500G>A)?

DNAJC6 p.Glu500= (c.1500G>A) is associated with juvenile onset Parkinson disease 19A (ClinVar).

How is Atypical juvenile parkinsonism inherited?

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

DNAJC6 p.Glu500=

Q: How common is DNAJC6 p.Glu500= (c.1500G>A) in the general population?

DNAJC6 p.Glu500= (c.1500G>A) is common (popmax 53.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1500G>A · rs4325172 · VCV1170299

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 53.7%, nfe) — too common for a highly-penetrant pathogenic allele

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 2.1	GERP 4.5, phastCons 1
Overall
CADD	6.102	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 53.7% European (non-Finnish) · 631,017/1,176,026 alleles

Filtering AF 53.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 53.5%

Overall 50% 803,859/1,607,310 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	53.7%	2
Ashkenazi Jewishnot grpmax-eligible	53.5%	2
Amishnot grpmax-eligible	52.5%	2
Middle Eastern	52.1%	2
Remaining individualsnot grpmax-eligible	48.2%	2
Admixed American	47.2%	2
Finnishnot grpmax-eligible	43.7%	2
South Asian	40.8%	2
African / African-American	30.2%	3
East Asian	18.7%	5

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.Glu500=
Coding: c.1500G>A
MANE Select: NM_001256864
dbSNP: rs4325172
Type: single nucleotide variant
Location: chr1:65392462 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.29
Residue 500: 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-glu500 (accessed [today's date]).

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