Is DNAJC19 p.Ala64= (c.192A>G) pathogenic?

DNAJC19 p.Ala64= (c.192A>G) is classified Likely benign in DNAJC19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-07). Very rare (popmax 0.00446%, eas); Associated with 3-methylglutaconic aciduria type 5.

What condition is associated with DNAJC19 p.Ala64= (c.192A>G)?

DNAJC19 p.Ala64= (c.192A>G) is associated with 3-methylglutaconic aciduria type 5 (ClinVar).

How common is DNAJC19 p.Ala64= (c.192A>G) in the general population?

DNAJC19 p.Ala64= (c.192A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

How is Dilated cardiomyopathy with ataxia inherited?

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

DNAJC19 p.Ala64=

c.192A>G · rs1473896211 · VCV632790

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 0.16	GERP -2.3, phastCons 0.99
Overall
CADD	10.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,836 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000186% 3/1,613,890 alleles · very rare exomes 3/1,461,556 · genomes 0/152,334 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,418
European (non-Finnish)	8.48e-05%	1,179,812

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.Ala64=
Coding: c.192A>G
MANE Select: NM_145261
dbSNP: rs1473896211
Type: single nucleotide variant
Location: chr3:180986960 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.50
Residue 64: 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 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-ala64 (accessed [today's date]).

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