Is DNAJB2 p.Arg283Trp (c.847C>T) pathogenic?

DNAJB2 p.Arg283Trp (c.847C>T) is classified Uncertain significance in DNAJB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). AlphaMissense: likely benign (0.0733); Very rare (popmax 0.00801%, afr).

How common is DNAJB2 p.Arg283Trp (c.847C>T) in the general population?

DNAJB2 p.Arg283Trp (c.847C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about DNAJB2 p.Arg283Trp (c.847C>T)?

AlphaMissense predicts likely benign (score 0.0733) — an in-silico prediction, not a clinical call.

DNAJB2 p.Arg283Trp

c.847C>T · rs769473223 · VCV1695005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0733 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0733	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -9.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.14	GERP -3.3, phastCons 0.008
Regional constraint	o/e 0.85	unconstrained · MANE · 5,150 bp · p 0.0024 · regional, not allelic
Overall
CADD	20.2	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,910 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00149% 24/1,609,780 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,485
Admixed American	0.00335%	29,814
European (non-Finnish)	0.00127%	78,532
South Asian	0.0011%	90,698

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: DNAJB2
Protein: p.Arg283Trp
Coding: c.847C>T
MANE Select: NM_006736
dbSNP: rs769473223
Type: single nucleotide variant
Location: chr2:219284859 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.73 · 1 PDB
Residue 283: the 'disordered' region

Full DNAJB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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DNAJB2 p.Arg104Gln Uncertain significance ★★ ⚠ same type
DNAJB2 p.Arg165Cys Uncertain significance ★★ ⚠ same type
DNAJB2 p.Arg178His Uncertain significance ★★ ⚠ same type
DNAJB2 p.Arg182Cys Uncertain significance ★★ ⚠ same type
DNAJB2 p.Arg191Gln 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/dnajb2-p-arg283trp (accessed [today's date]).

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