Is DNAJB11 p.Arg289Trp (c.865C>T) pathogenic?

DNAJB11 p.Arg289Trp (c.865C>T) is classified Uncertain significance in DNAJB11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-17). AlphaMissense: likely pathogenic (0.7432); Ultra-rare (popmax 0.0104%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DNAJB11 p.Arg289Trp (c.865C>T)?

DNAJB11 p.Arg289Trp (c.865C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAJB11 p.Arg289Trp (c.865C>T) in the general population?

DNAJB11 p.Arg289Trp (c.865C>T) is ultra-rare (popmax 0.0104%, nfe) (gnomAD).

What do computational predictors say about DNAJB11 p.Arg289Trp (c.865C>T)?

AlphaMissense predicts likely pathogenic (score 0.7432) — an in-silico prediction, not a clinical call.

DNAJB11 p.Arg289Trp

c.865C>T · rs201669927 · VCV1306202

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7432 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0104%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7432	likely pathogenic
REVEL	0.568	indeterminate
SaProt	LLR -13.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 15 kb · p 7.3e-05 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0104% European (non-Finnish) · 120/1,157,418 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00827%

Overall 0.00851% 132/1,551,824 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0104%	9,645
Finnishnot grpmax-eligible	0.00791%	12,643
Remaining individualsnot grpmax-eligible	0.00501%	19,953
East Asian	0.00238%	42,098
Admixed American	0.00226%	44,320
African / African-American	0.00142%	70,606
South Asian	0.00124%	80,432

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: DNAJB11
Protein: p.Arg289Trp
Coding: c.865C>T
MANE Select: NM_016306
dbSNP: rs201669927
Type: single nucleotide variant
Location: chr3:186584442 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.34
Residue 289: a UniProt-annotated variant site (in pkd6)

Full DNAJB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DNAJB11 p.Arg289Gln Uncertain significance ★ ⚠ same residue
DNAJB11 p.Thr188Ser Uncertain significance ★★ ⚠ same condition
DNAJB11 p.Thr8Ile Uncertain significance ★★ ⚠ same condition
DNAJB11 p.Ala147Val Uncertain significance ★ ⚠ same condition
DNAJB11 p.Ala163Ser Uncertain significance ★ ⚠ same condition
DNAJB11 p.Ala19Val Uncertain significance ★ ⚠ same condition
DNAJB11 p.Arg167Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
DNAJB11 p.Arg176Gln 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/dnajb11-p-arg289trp (accessed [today's date]).

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