Is DNAJC19 p.Lys116= (c.348A>G) pathogenic?

DNAJC19 p.Lys116= (c.348A>G) is classified Likely benign in DNAJC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-07). Very rare (popmax 0.00111%, sas); Associated with 3-methylglutaconic aciduria type 5.

What condition is associated with DNAJC19 p.Lys116= (c.348A>G)?

DNAJC19 p.Lys116= (c.348A>G) is associated with 3-methylglutaconic aciduria type 5 (ClinVar).

How common is DNAJC19 p.Lys116= (c.348A>G) in the general population?

DNAJC19 p.Lys116= (c.348A>G) is very rare (popmax 0.00111%, 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.Lys116=

c.348A>G · rs771098271 · VCV1640522

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Conditions

3-methylglutaconic aciduria type 5

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
Pangolin	Δ0.24	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 1.2	GERP 2, phastCons 1
Overall
CADD	9.789	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% South Asian · 1/90,086 alleles

Overall 6.91e-05% 1/1,447,968 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.Lys116=
Coding: c.348A>G
MANE Select: NM_145261
dbSNP: rs771098271
Type: single nucleotide variant
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.Lys116fs Uncertain significance ★ same residue
DNAJC19 c.130-1G>C Pathogenic ★★ same condition
DNAJC19 c.4-1G>A Likely pathogenic ★★ same condition
DNAJC19 c.55+1G>A Pathogenic/Likely pathogenic ★★ same condition
DNAJC19 p.Ala25Thr Uncertain significance ★★ ⚠ same condition
DNAJC19 p.Ala73Thr Uncertain significance ★★ same condition
DNAJC19 p.Arg84Gln Uncertain significance ★★ ⚠ same condition
DNAJC19 p.Gly68Asp 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/dnajc19-p-lys116 (accessed [today's date]).

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