Is DNAJB11 p.Arg289Gln (c.866G>A) pathogenic?

DNAJB11 p.Arg289Gln (c.866G>A) is classified Uncertain significance in DNAJB11 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-11-11). AlphaMissense: likely pathogenic (0.5653); Ultra-rare (popmax 0.0119%, eas).

How common is DNAJB11 p.Arg289Gln (c.866G>A) in the general population?

DNAJB11 p.Arg289Gln (c.866G>A) is ultra-rare (popmax 0.0119%, eas) (gnomAD).

What do computational predictors say about DNAJB11 p.Arg289Gln (c.866G>A)?

AlphaMissense predicts likely pathogenic (score 0.5653) — an in-silico prediction, not a clinical call.

DNAJB11 p.Arg289Gln

c.866G>A · rs758228321 · VCV1940548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5653 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5653	likely pathogenic
REVEL	0.437	indeterminate
SaProt	LLR -11.25	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 9.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 15 kb · p 7.3e-05 · regional, not allelic
Overall
CADD	32.0	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 0.0119% East Asian · 5/42,074 alleles

Filtering AF 0.00468% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.000644% 10/1,553,496 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0119%	8,415
African / African-American	0.00142%	70,664
South Asian	0.00124%	80,814
European (non-Finnish)	0.000259%	386,091

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.Arg289Gln
Coding: c.866G>A
MANE Select: NM_016306
dbSNP: rs758228321
Type: single nucleotide variant
Location: chr3:186584443 (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

Similar variants

DNAJB11 p.Arg289Trp Uncertain significance ★★ ⚠ same residue
DNAJB11 p.Arg206Ter Pathogenic ★★ same type
DNAJB11 p.Arg242Ter Pathogenic ★★ same type
DNAJB11 p.Arg24Ter Pathogenic ★★ same type
DNAJB11 p.Arg34Ter Pathogenic ★★ same type
DNAJB11 p.Glu144Ter Pathogenic/Likely pathogenic ★★ same type
DNAJB11 p.Leu77Pro Likely pathogenic ★★ same type
DNAJB11 p.Pro54Arg Likely pathogenic ★★ 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/dnajb11-p-arg289gln (accessed [today's date]).

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