Is DNAJC19 p.Tyr21Ter (c.62dup) pathogenic?

DNAJC19 p.Tyr21Ter (c.62dup) is classified Pathogenic in DNAJC19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-23). Very rare (popmax 0.0011%, sas); Associated with 3-methylglutaconic aciduria type 5.

What condition is associated with DNAJC19 p.Tyr21Ter (c.62dup)?

DNAJC19 p.Tyr21Ter (c.62dup) is associated with 3-methylglutaconic aciduria type 5 (ClinVar).

How common is DNAJC19 p.Tyr21Ter (c.62dup) in the general population?

DNAJC19 p.Tyr21Ter (c.62dup) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Dilated cardiomyopathy with ataxia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DNAJC19 p.Tyr21Ter

c.62dup · rs1560040369 · VCV1299515

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

3-methylglutaconic aciduria type 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.52	GERP -3.7, phastCons 0.76
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,080 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00062% 10/1,613,972 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00312%	32,010
South Asiangrpmax	0.0011%	91,080
European (non-Finnish)	0.000593%	168,572

Finnish 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: DNAJC19
Protein: p.Tyr21Ter
Coding: c.62dup
MANE Select: NM_145261
dbSNP: rs1560040369
Type: Duplication
Location: chr3:180988089 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.50

Full DNAJC19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

3-methylglutaconic aciduria type 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dilated cardiomyopathy with ataxia (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

DNAJC19 p.Tyr21= Likely benign ★★ same residue
DNAJC19 p.Lys57fs Pathogenic ★ same condition
DNAJC19 c.280+2dup Conflicting classifications of pathogenicity ★ same condition
DNAJC19 p.Ile103fs Uncertain significance ★ same condition
DNAJC19 p.Ile99fs Uncertain significance ★ same condition
DNAJC19 p.Tyr21Phe Uncertain significance ★ ⚠ same residue
DNAJC19 c.281-15dup Benign ★ same condition
DNAJC19 c.130-1G>C Pathogenic ★★ 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/dnajc19-p-tyr21ter (accessed [today's date]).

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