Is DNAJB5 p.Arg235Trp (c.703C>T) pathogenic?

DNAJB5 p.Arg235Trp (c.703C>T) is classified Uncertain significance in DNAJB5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.3305); Very rare (popmax 0.00833%, amr).

How common is DNAJB5 p.Arg235Trp (c.703C>T) in the general population?

DNAJB5 p.Arg235Trp (c.703C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about DNAJB5 p.Arg235Trp (c.703C>T)?

AlphaMissense predicts likely benign (score 0.3305) — an in-silico prediction, not a clinical call.

DNAJB5 p.Arg235Trp

c.703C>T · VCV4661276

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3305 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3305	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -11.80	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.74, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 3,966 bp · p 2.3e-20 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R163W vs ClinVar R235W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,002 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00062% 10/1,614,022 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,000
East Asian	0.00223%	44,880
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00156%	64,038
European (non-Finnish)	0.000169%	590,016

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: DNAJB5
Protein: p.Arg235Trp
Coding: c.703C>T
MANE Select: NM_001349723
Type: single nucleotide variant
Location: chr9:34996540 (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-arg235trp (accessed [today's date]).

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