Is DNAJB2 p.Ala14Val (c.41C>T) pathogenic?

DNAJB2 p.Ala14Val (c.41C>T) is classified Uncertain significance in DNAJB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-26). AlphaMissense: likely pathogenic (0.931); Very rare (popmax 0.00178%, nfe); Associated with neuronopathy, distal hereditary motor, autosomal recessive 5.

What condition is associated with DNAJB2 p.Ala14Val (c.41C>T)?

DNAJB2 p.Ala14Val (c.41C>T) is associated with neuronopathy, distal hereditary motor, autosomal recessive 5 (ClinVar).

How common is DNAJB2 p.Ala14Val (c.41C>T) in the general population?

DNAJB2 p.Ala14Val (c.41C>T) is very rare (popmax 0.00178%, nfe) (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.

What do computational predictors say about DNAJB2 p.Ala14Val (c.41C>T)?

AlphaMissense predicts likely pathogenic (score 0.931) — an in-silico prediction, not a clinical call.

DNAJB2 p.Ala14Val

c.41C>T · rs1340065979 · VCV1496363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.931 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neuronopathy, distal hereditary motor, autosomal recessive 5

Computational evidence

Protein change
AlphaMissense	0.931	likely pathogenic
REVEL	0.364	indeterminate
SaProt	LLR -12.95	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 5,150 bp · p 0.0024 · regional, not allelic
Overall
CADD	26.6	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 0.00178% European (non-Finnish) · 21/1,179,978 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.0013% 21/1,613,846 alleles · very rare

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.Ala14Val
Coding: c.41C>T
MANE Select: NM_006736
dbSNP: rs1340065979
Type: single nucleotide variant
Location: chr2:219279874 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.73 · 1 PDB
Residue 14: the j domain

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.Ala14Thr 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-ala14val (accessed [today's date]).

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