Is DNAJC6 p.Ser720Leu (c.2159C>T) pathogenic?

DNAJC6 p.Ser720Leu (c.2159C>T) is classified Likely benign in DNAJC6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-19). AlphaMissense: likely benign (0.0639); Rare (popmax 0.404%, afr); Associated with juvenile onset Parkinson disease 19A.

What condition is associated with DNAJC6 p.Ser720Leu (c.2159C>T)?

DNAJC6 p.Ser720Leu (c.2159C>T) is associated with juvenile onset Parkinson disease 19A (ClinVar).

How common is DNAJC6 p.Ser720Leu (c.2159C>T) in the general population?

DNAJC6 p.Ser720Leu (c.2159C>T) is rare (popmax 0.404%, afr) (gnomAD).

How is Atypical juvenile parkinsonism inherited?

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

What do computational predictors say about DNAJC6 p.Ser720Leu (c.2159C>T)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

DNAJC6 p.Ser720Leu

c.2159C>T · rs143504255 · VCV1196512

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.404%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

juvenile onset Parkinson disease 19A

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -7.39	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	GERP 4.6
Regional constraint	o/e 0.85	unconstrained · MANE · 103 kb · p 3.7e-07 · regional, not allelic
Overall
CADD	16.97	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S663L vs ClinVar S720L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.404% African / African-American · 303/75,014 alleles

Filtering AF 0.367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.352%

Overall 0.0225% 363/1,613,938 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.404%	248
Middle Eastern	0.0495%	2,021
Admixed American	0.0417%	2,399
Remaining individualsnot grpmax-eligible	0.0304%	3,289
South Asian	0.0011%	91,052
European (non-Finnish)	0.00102%	98,331

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.Ser720Leu
Coding: c.2159C>T
MANE Select: NM_001256864
dbSNP: rs143504255
Type: single nucleotide variant
Location: chr1:65401812 (GRCh38)
Gene constraint: LOEUF 0.416 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 64.29
Residue 720: 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-ser720leu (accessed [today's date]).

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