Is DNAJC19 p.Ile99fs (c.295dup) pathogenic?

DNAJC19 p.Ile99fs (c.295dup) is classified Uncertain significance in DNAJC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). Very rare (popmax 0.000425%, nfe); Associated with 3-methylglutaconic aciduria type 5.

What condition is associated with DNAJC19 p.Ile99fs (c.295dup)?

DNAJC19 p.Ile99fs (c.295dup) is associated with 3-methylglutaconic aciduria type 5 (ClinVar).

How common is DNAJC19 p.Ile99fs (c.295dup) in the general population?

DNAJC19 p.Ile99fs (c.295dup) is very rare (popmax 0.000425%, nfe) (gnomAD).

How is Dilated cardiomyopathy with ataxia inherited?

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

DNAJC19 p.Ile99fs

c.295dup · rs761342359 · VCV2185705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000425%, nfe)

Conditions

3-methylglutaconic aciduria type 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.3	GERP 2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000425% European (non-Finnish) · 5/1,175,354 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000311% 5/1,607,354 alleles · very rare exomes 5/1,455,048 · genomes 0/152,306 · joint denominator

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.Ile99fs
Coding: c.295dup
MANE Select: NM_145261
dbSNP: rs761342359
Type: Duplication
Location: chr3:180984695 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.50
Residue 99: the j domain

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.Ile99Val Uncertain significance ★★ ⚠ same residue
DNAJC19 p.Tyr21Ter Pathogenic ★★ same condition
DNAJC19 p.Lys57fs Pathogenic ★ same condition
DNAJC19 c.280+2dup Conflicting classifications of pathogenicity ★ same condition
DNAJC19 p.Ile103fs Uncertain significance ★ same condition
DNAJC19 c.281-15dup Benign ★ same condition
DNAJC19 c.130-1G>C Pathogenic ★★ same condition
DNAJC19 c.280+1_280+5del Likely 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-ile99fs (accessed [today's date]).

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