Is DNAJB2 p.Tyr261= (c.783C>T) pathogenic?

DNAJB2 p.Tyr261= (c.783C>T) is classified Likely benign in DNAJB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-02). Very rare (popmax 0.00801%, afr); Associated with neuronopathy, distal hereditary motor, autosomal recessive 5.

What condition is associated with DNAJB2 p.Tyr261= (c.783C>T)?

DNAJB2 p.Tyr261= (c.783C>T) is associated with neuronopathy, distal hereditary motor, autosomal recessive 5 (ClinVar).

How common is DNAJB2 p.Tyr261= (c.783C>T) in the general population?

DNAJB2 p.Tyr261= (c.783C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

How is DNAJB2-related Charcot-Marie-Tooth disease type 2 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DNAJB2 p.Tyr261=

c.783C>T · rs762593270 · VCV1572599

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Conditions

neuronopathy, distal hereditary motor, autosomal recessive 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 0.5, phastCons 1
Overall
CADD	9.074	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,936 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.000744% 12/1,612,982 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,489
Remaining individualsnot grpmax-eligible	0.0016%	62,458
European (non-Finnish)	0.000424%	235,949

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.Tyr261=
Coding: c.783C>T
MANE Select: NM_006736
dbSNP: rs762593270
Type: single nucleotide variant
Location: chr2:219284795 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.73 · 1 PDB
Residue 261: the uim 2 domain; the 'disordered' region

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

Disease context

neuronopathy, distal hereditary motor, autosomal recessive 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For DNAJB2-related Charcot-Marie-Tooth disease type 2 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult

Similar variants

DNAJB2 p.Tyr261Cys Uncertain significance ★ ⚠ same residue
DNAJB2 c.175+2T>A Pathogenic/Likely pathogenic ★★ same condition
DNAJB2 c.352+1G>A Pathogenic ★★ same condition
DNAJB2 c.65+1G>A Likely pathogenic ★★ same condition
DNAJB2 p.Arg104Gln Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg165Cys Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg178His Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg182Cys 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/dnajb2-p-tyr261 (accessed [today's date]).

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