Is DNAJB2 p.Leu263= (c.787C>T) pathogenic?

DNAJB2 p.Leu263= (c.787C>T) is classified Likely benign in DNAJB2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-19). Ultra-rare (popmax 0.0649%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DNAJB2 p.Leu263= (c.787C>T)?

DNAJB2 p.Leu263= (c.787C>T) is associated with Inborn genetic diseases, neuronopathy, distal hereditary motor, autosomal recessive 5, Charcot-Marie-Tooth disease (ClinVar).

How common is DNAJB2 p.Leu263= (c.787C>T) in the general population?

DNAJB2 p.Leu263= (c.787C>T) is ultra-rare (popmax 0.0649%, nfe) (gnomAD).

DNAJB2 p.Leu263=

c.787C>T · rs140805390 · VCV377780

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0649%, nfe)

Conditions

Inborn genetic diseases

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 2.2	GERP -1.3, phastCons 1
Overall
CADD	9.477	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0649% European (non-Finnish) · 766/1,179,700 alleles

Filtering AF 0.0611% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0596%

Overall 0.0582% 939/1,613,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.228%	438
European (non-Finnish)grpmax	0.0649%	1,540
Remaining individualsnot grpmax-eligible	0.0352%	2,840
African / African-American	0.00666%	15,012
Admixed American	0.00167%	59,950

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: DNAJB2
Protein: p.Leu263=
Coding: c.787C>T
MANE Select: NM_006736
dbSNP: rs140805390
Type: single nucleotide variant
Location: chr2:219284799 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.73 · 1 PDB
Residue 263: the uim 2 domain; the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuronopathy, distal hereditary motor, autosomal recessive 5 Charcot-Marie-Tooth disease

Similar variants

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
DNAJB2 p.Arg191Gln 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-leu263 (accessed [today's date]).

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