Is DNAJC19 c.280+5G>C pathogenic?

DNAJC19 c.280+5G>C is classified Uncertain significance in DNAJC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-21). Ultra-rare (popmax 0.0582%, sas); Associated with 3-methylglutaconic aciduria type 5.

What condition is associated with DNAJC19 c.280+5G>C?

DNAJC19 c.280+5G>C is associated with 3-methylglutaconic aciduria type 5 (ClinVar).

How common is DNAJC19 c.280+5G>C in the general population?

DNAJC19 c.280+5G>C is ultra-rare (popmax 0.0582%, sas) (gnomAD).

How is Dilated cardiomyopathy with ataxia inherited?

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

DNAJC19 c.280+5G>C

rs762722601 · VCV1444627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0582%, 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
Splice region	donor +5	donor splice region (+5, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.82, phastCons 1
Non-coding constraint	Z 1.52	1 kb window · o/e 0.89 · regional · uncalibrated
Overall
CADD	19.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0582% South Asian · 53/91,054 alleles

Filtering AF 0.0457% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0412%

Overall 0.00335% 54/1,612,446 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0582%	1,718
Remaining individualsnot grpmax-eligible	0.0016%	62,432

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
Coding: c.280+5G>C
MANE Select: NM_145261
dbSNP: rs762722601
Type: single nucleotide variant
Location: chr3:180985921 (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-c-280-plus-5g-c (accessed [today's date]).

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