Is DNAJB5 p.Lys385Arg (c.1154A>G) pathogenic?

DNAJB5 p.Lys385Arg (c.1154A>G) is classified Uncertain significance in DNAJB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1067); Absent from gnomAD v4.1.

How common is DNAJB5 p.Lys385Arg (c.1154A>G) in the general population?

DNAJB5 p.Lys385Arg (c.1154A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJB5 p.Lys385Arg (c.1154A>G)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

DNAJB5 p.Lys385Arg

c.1154A>G · VCV4661283

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -7.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 3,966 bp · p 2.3e-20 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM K313R vs ClinVar K385R) — verify the residue.

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: DNAJB5
Protein: p.Lys385Arg
Coding: c.1154A>G
MANE Select: NM_001349723
Type: single nucleotide variant
Location: chr9:34997150 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 80.69

Full DNAJB5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB5 p.Arg277His Uncertain significance ★★ ⚠ same type
DNAJB5 p.Glu141= Uncertain significance ★★ same type
DNAJB5 p.Thr406Pro Uncertain significance ★★ ⚠ same type
DNAJB5 c.40G>A Uncertain significance ★ same type
DNAJB5 c.50T>C Uncertain significance ★ same type
DNAJB5 c.55G>C Uncertain significance ★ same type
DNAJB5 c.58C>T Uncertain significance ★ same type
DNAJB5 c.-133+6G>A 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/dnajb5-p-lys385arg (accessed [today's date]).

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