Is DNAJC19 p.Leu23= (c.69G>A) pathogenic?

DNAJC19 p.Leu23= (c.69G>A) is classified Benign/Likely benign in DNAJC19 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-01). Low-frequency (popmax 2.47%, mid); Associated with 3-methylglutaconic aciduria type 5.

What condition is associated with DNAJC19 p.Leu23= (c.69G>A)?

DNAJC19 p.Leu23= (c.69G>A) is associated with 3-methylglutaconic aciduria type 5 (ClinVar).

How common is DNAJC19 p.Leu23= (c.69G>A) in the general population?

DNAJC19 p.Leu23= (c.69G>A) is low-frequency (popmax 2.47%, mid) (gnomAD).

How is Dilated cardiomyopathy with ataxia inherited?

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

DNAJC19 p.Leu23=

c.69G>A · rs142023670 · VCV137120

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.47%, mid)

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
Constraint at this position
Conservation	phyloP 1.8	GERP 0.24, phastCons 1
Overall
CADD	10.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.47% Middle Eastern · 150/6,062 alleles

Filtering AF 2.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.03%

Overall 0.388% 6,257/1,614,120 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.47%	40
South Asian	0.969%	103
Admixed American	0.741%	135
Ashkenazi Jewishnot grpmax-eligible	0.527%	190
Remaining individualsnot grpmax-eligible	0.499%	200
European (non-Finnish)	0.359%	278
African / African-American	0.0746%	1,340
Finnishnot grpmax-eligible	0.0219%	4,573
East Asian	0.00223%	44,874

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.Leu23=
Coding: c.69G>A
MANE Select: NM_145261
dbSNP: rs142023670
Type: single nucleotide variant
Location: chr3:180988083 (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 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
DNAJC19 p.Gly68Ser 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-leu23 (accessed [today's date]).

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