Is DNAJC3 p.Arg346Ter (c.1036C>T) pathogenic?

DNAJC3 p.Arg346Ter (c.1036C>T) is classified Pathogenic in DNAJC3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-06-23). Very rare (popmax 8.48e-05%, nfe); Associated with juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome.

How common is DNAJC3 p.Arg346Ter (c.1036C>T) in the general population?

DNAJC3 p.Arg346Ter (c.1036C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

DNAJC3 p.Arg346Ter

Q: What condition is associated with DNAJC3 p.Arg346Ter (c.1036C>T)?

DNAJC3 p.Arg346Ter (c.1036C>T) is associated with juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome (ClinVar).

Q: How is Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome inherited?

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

c.1036C>T · rs1594013989 · VCV1693488

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.8, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,936 alleles

Overall 6.84e-05% 1/1,461,734 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: DNAJC3
Protein: p.Arg346Ter
Coding: c.1036C>T
MANE Select: NM_006260
dbSNP: rs1594013989
Type: single nucleotide variant
Location: chr13:95763914 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.78 · 2 PDB
Residue 346: an α-helix

Full DNAJC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy

Similar variants

DNAJC3 p.Arg346Gln Uncertain significance ★ ⚠ same residue
DNAJC3 p.Arg346= Likely benign ★ same residue
DNAJC3 p.Arg393Ter Pathogenic/Likely pathogenic ★★ same condition
DNAJC3 c.729-1G>A Uncertain significance ★ same condition
DNAJC3 p.Arg415Ter Conflicting classifications of pathogenicity ★ same condition
DNAJC3 c.393+2T>C Pathogenic same condition
DNAJC3 c.393+2T>G Pathogenic same condition
DNAJC3 p.Met1Val 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/dnajc3-p-arg346ter (accessed [today's date]).

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