Is DNAJB5 p.Pro15Ser (c.43C>T) pathogenic?

DNAJB5 p.Pro15Ser (c.43C>T) is classified Conflicting classifications of pathogenicity in DNAJB5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2019-12-01). Ultra-rare (popmax 0.0167%, nfe); Associated with peripheral neuropathy.

What condition is associated with DNAJB5 p.Pro15Ser (c.43C>T)?

DNAJB5 p.Pro15Ser (c.43C>T) is associated with peripheral neuropathy, skeletal muscle disorder (ClinVar).

How common is DNAJB5 p.Pro15Ser (c.43C>T) in the general population?

DNAJB5 p.Pro15Ser (c.43C>T) is ultra-rare (popmax 0.0167%, nfe) (gnomAD).

DNAJB5 p.Pro15Ser

c.43C>T · rs774909609 · VCV243086

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, nfe)

Conditions

peripheral neuropathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.07	moderately benign-leaning
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.84	GERP -0.23, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 2,658 bp · p 0.88 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0167% European (non-Finnish) · 192/1,147,008 alleles

Filtering AF 0.0148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.014%

Overall 0.013% 201/1,551,582 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0167%	5,974
Finnishnot grpmax-eligible	0.00668%	14,978
Admixed American	0.00392%	25,494
African / African-American	0.00274%	36,510
Remaining individualsnot grpmax-eligible	0.00166%	60,094

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.Pro15Ser
Coding: c.43C>T
MANE Select: NM_001349723
dbSNP: rs774909609
Type: single nucleotide variant
Location: chr9:34990673 (GRCh38)
Gene constraint: LOEUF 0.605 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 80.69
Residue 15: the j domain

Full DNAJB5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peripheral neuropathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: skeletal muscle disorder

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-pro15ser (accessed [today's date]).

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