Is DNAJC19 p.Lys116fs (c.348del) pathogenic?

DNAJC19 p.Lys116fs (c.348del) is classified Uncertain significance in DNAJC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-15). Very rare (popmax 0.00168%, amr); Associated with 3-methylglutaconic aciduria type 5.

What condition is associated with DNAJC19 p.Lys116fs (c.348del)?

DNAJC19 p.Lys116fs (c.348del) is associated with 3-methylglutaconic aciduria type 5 (ClinVar).

How common is DNAJC19 p.Lys116fs (c.348del) in the general population?

DNAJC19 p.Lys116fs (c.348del) is very rare (popmax 0.00168%, amr) (gnomAD).

How is Dilated cardiomyopathy with ataxia inherited?

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

DNAJC19 p.Lys116fs

c.348del · rs1714802157 · VCV1045827

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 0.00168%, amr)

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 11	GERP 2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00168% Admixed American · 1/59,432 alleles

Overall 6.91e-05% 1/1,448,160 alleles · very rare

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.Lys116fs
Coding: c.348del
MANE Select: NM_145261
dbSNP: rs1714802157
Type: Deletion
Location: chr3:180984643 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.50
Residue 116: 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.Lys116= Likely benign ★ same residue
DNAJC19 c.280+1_280+5del Likely pathogenic ★★ same condition
DNAJC19 p.Arg20_Tyr21insTer Pathogenic/Likely pathogenic ★★ same condition
DNAJC19 c.4-24_15del Likely pathogenic ★ same condition
DNAJC19 p.Ala101fs Likely pathogenic ★ same condition
DNAJC19 p.Leu10fs Pathogenic ★ same condition
DNAJC19 p.Leu87_Leu88insTer Pathogenic ★ same condition
DNAJC19 p.Lys34fs 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-lys116fs (accessed [today's date]).

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