Is DNAJB4 p.Arg25Ter (c.73C>T) pathogenic?

DNAJB4 p.Arg25Ter (c.73C>T) is classified Likely benign in DNAJB4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-02-27). Low-frequency (popmax 3.54%, afr); Associated with DNAJB4-related disorder.

What condition is associated with DNAJB4 p.Arg25Ter (c.73C>T)?

DNAJB4 p.Arg25Ter (c.73C>T) is associated with DNAJB4-related disorder (ClinVar).

How common is DNAJB4 p.Arg25Ter (c.73C>T) in the general population?

DNAJB4 p.Arg25Ter (c.73C>T) is low-frequency (popmax 3.54%, afr) (gnomAD).

DNAJB4 p.Arg25Ter

c.73C>T · rs149535846 · VCV3039041

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 3.54%, afr)

Conditions

DNAJB4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	0.322	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 3.54% African / African-American · 1,467/41,488 alleles

Filtering AF 3.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.32%

Overall 1.01% 1,543/152,066 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.54%	28
Remaining individualsnot grpmax-eligible	0.568%	176
Admixed American	0.347%	288
Middle Eastern	0.338%	296
South Asian	0.0207%	4,820
European (non-Finnish)	0.0132%	7,561

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: DNAJB4
Protein: p.Arg25Ter
Coding: c.73C>T
MANE Select: NM_007034 · reported on NM_001317100
dbSNP: rs149535846
Type: single nucleotide variant
Location: chr1:77992848 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.68 (gnomAD)
Structure: AlphaFold pLDDT 83.43
Residue 25: the j domain; a UniProt-annotated variant site (in cmyo21; loss of function in chaperone-mediated protein folding; in cells subjected to heat shock, it results in increased protein aggregation and cell death compared to the wild type; unable to complement growth defects in a yeast complementation assay; does not affect subcellular location at the z line)

Full DNAJB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DNAJB4-related disorder

Similar variants

DNAJB4 p.Arg25Gln Pathogenic same residue
DNAJB4 p.Pro33Leu Uncertain significance ⚠ same condition
DNAJB4 p.Asp309Ter Uncertain significance same condition
DNAJB4 p.Ala76Pro Uncertain significance ★ ⚠ same type
DNAJB4 p.Arg146Ser Uncertain significance ★ ⚠ same type
DNAJB4 p.Arg153His Uncertain significance ★ ⚠ same type
DNAJB4 p.Arg178Gln Uncertain significance ★ ⚠ same type
DNAJB4 p.Arg245Ser Uncertain significance ★ ⚠ same type

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/dnajb4-p-arg25ter (accessed [today's date]).

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