Is DNAJB4 p.Lys286Ter (c.856A>T) pathogenic?

DNAJB4 p.Lys286Ter (c.856A>T) is classified Pathogenic in DNAJB4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-16). Absent from gnomAD v4.1; Associated with congenital myopathy 21 with early respiratory failure.

What condition is associated with DNAJB4 p.Lys286Ter (c.856A>T)?

DNAJB4 p.Lys286Ter (c.856A>T) is associated with congenital myopathy 21 with early respiratory failure (ClinVar).

How common is DNAJB4 p.Lys286Ter (c.856A>T) in the general population?

DNAJB4 p.Lys286Ter (c.856A>T) is absent from gnomAD v4.1 (gnomAD).

DNAJB4 p.Lys286Ter

c.856A>T · rs2524296398 · VCV2499482

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital myopathy 21 with early respiratory failure

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	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	37.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAJB4
Protein: p.Lys286Ter
Coding: c.856A>T
MANE Select: NM_007034
dbSNP: rs2524296398
Type: single nucleotide variant
Location: chr1:78016089 (GRCh38)
Gene constraint: LOEUF 0.617 · pLI 0.68 (gnomAD)
Structure: AlphaFold pLDDT 83.43
Residue 286: a UniProt-annotated variant site (in cmyo21; severely decreased protein abundance in homozygous patient cells; increased degradation)

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

Disease context

congenital myopathy 21 with early respiratory failure — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAJB4 p.Arg25Gln Pathogenic same condition
DNAJB4 p.Arg61Gly Pathogenic same condition
DNAJB4 p.Leu262Ser Pathogenic 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-lys286ter (accessed [today's date]).

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