Is DNAJC6 p.Ala226= (c.678G>A) pathogenic?

DNAJC6 p.Ala226= (c.678G>A) is classified Benign/Likely benign in DNAJC6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Low-frequency (popmax 3.95%, mid); Associated with juvenile onset Parkinson disease 19A.

What condition is associated with DNAJC6 p.Ala226= (c.678G>A)?

DNAJC6 p.Ala226= (c.678G>A) is associated with juvenile onset Parkinson disease 19A (ClinVar).

How common is DNAJC6 p.Ala226= (c.678G>A) in the general population?

DNAJC6 p.Ala226= (c.678G>A) is low-frequency (popmax 3.95%, mid) (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.Ala226=

c.678G>A · rs61753391 · VCV474681

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.95%, mid)

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 -2.2	GERP -8.4
Overall
CADD	7.833	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.95% Middle Eastern · 227/5,744 alleles

Filtering AF 3.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.37%

Overall 2.31% 34,973/1,516,340 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	3.95%	25
European (non-Finnish)	2.64%	38
Finnishnot grpmax-eligible	2.37%	42
Remaining individualsnot grpmax-eligible	2.32%	43
Amishnot grpmax-eligible	1.97%	51
Ashkenazi Jewishnot grpmax-eligible	1.82%	55
Admixed American	1.55%	65
South Asian	0.656%	152
African / African-American	0.449%	223
East Asian	0.00518%	19,304

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.Ala226=
Coding: c.678G>A
MANE Select: NM_001256864
dbSNP: rs61753391
Type: single nucleotide variant
Location: chr1:65384204 (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.Ala226Val Uncertain significance ★★ ⚠ same residue
DNAJC6 p.Arg330Ter Pathogenic ★★ 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-ala226 (accessed [today's date]).

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