Is DNAJB6 p.Arg62Trp (c.184C>T) pathogenic?

DNAJB6 p.Arg62Trp (c.184C>T) is classified Uncertain significance in DNAJB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-12-22). AlphaMissense: likely pathogenic (0.997); Very rare (popmax 8.48e-05%, nfe).

How common is DNAJB6 p.Arg62Trp (c.184C>T) in the general population?

DNAJB6 p.Arg62Trp (c.184C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DNAJB6 p.Arg62Trp (c.184C>T)?

AlphaMissense predicts likely pathogenic (score 0.997) — an in-silico prediction, not a clinical call.

DNAJB6 p.Arg62Trp

c.184C>T · rs886043038 · VCV285188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.997 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.997	likely pathogenic · top 8% in DNAJB6
REVEL	0.787	moderately pathogenic-leaning
SaProt	LLR -15.24	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 8,817 bp · p 0.017 · regional, not allelic
Overall
CADD	34.0	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 8.48e-05% European (non-Finnish) · 1/1,179,922 alleles

Overall 0.000137% 2/1,461,596 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	63,958
European (non-Finnish)grpmax	8.48e-05%	1,179,922

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DNAJB6
Protein: p.Arg62Trp
Coding: c.184C>T
MANE Select: NM_058246
dbSNP: rs886043038
Type: single nucleotide variant
Location: chr7:157366510 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.04 · 4 PDB
Residue 62: the j domain; an α-helix; the 'interaction with hsp70' region

Full DNAJB6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB6 p.Phe89Ile Pathogenic ★★ same type
DNAJB6 p.Phe91Leu Pathogenic ★★ same type
DNAJB6 p.Phe91Val Pathogenic/Likely pathogenic ★★ same type
DNAJB6 p.Pro96Arg Pathogenic ★★ same type
DNAJB6 c.66-2A>G Uncertain significance ★★ same type
DNAJB6 c.-7G>A Uncertain significance ★★ same type
DNAJB6 p.Ala22Val Uncertain significance ★★ ⚠ same type
DNAJB6 p.Ala237Pro 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/dnajb6-p-arg62trp (accessed [today's date]).

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