Is DNAJC6 p.Ser675= (c.2025G>A) pathogenic?

DNAJC6 p.Ser675= (c.2025G>A) is classified Benign in DNAJC6 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-06-11). Ultra-rare (popmax 0.0112%, eas); Associated with juvenile onset Parkinson disease 19A.

What condition is associated with DNAJC6 p.Ser675= (c.2025G>A)?

DNAJC6 p.Ser675= (c.2025G>A) is associated with juvenile onset Parkinson disease 19A (ClinVar).

How common is DNAJC6 p.Ser675= (c.2025G>A) in the general population?

DNAJC6 p.Ser675= (c.2025G>A) is ultra-rare (popmax 0.0112%, 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.Ser675=

c.2025G>A · rs185245369 · VCV2051812

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	GERP -7.7, phastCons 0.002
Overall
CADD	1.454	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% East Asian · 5/44,448 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00278%

Overall 0.00907% 146/1,609,938 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.308%	324
Remaining individualsnot grpmax-eligible	0.0192%	5,200
East Asiangrpmax	0.0112%	8,890
Admixed American	0.00337%	29,645
European (non-Finnish)	0.00288%	34,668
African / African-American	0.00134%	74,628
South Asian	0.00111%	89,992

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser675=
Coding: c.2025G>A
MANE Select: NM_001256864
dbSNP: rs185245369
Type: single nucleotide variant
Location: chr1:65395019 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.29
Residue 675: 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.Ser675Leu 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-ser675 (accessed [today's date]).

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