Is DNAJB2 p.Asp9Glu (c.27C>A) pathogenic?

DNAJB2 p.Asp9Glu (c.27C>A) is classified Uncertain significance in DNAJB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.2008); Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DNAJB2 p.Asp9Glu (c.27C>A)?

DNAJB2 p.Asp9Glu (c.27C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DNAJB2 p.Asp9Glu (c.27C>A) in the general population?

DNAJB2 p.Asp9Glu (c.27C>A) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about DNAJB2 p.Asp9Glu (c.27C>A)?

AlphaMissense predicts likely benign (score 0.2008) — an in-silico prediction, not a clinical call.

DNAJB2 p.Asp9Glu

c.27C>A · VCV4013524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2008 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2008	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -4.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -4.7, phastCons 0.45
Regional constraint	o/e 0.85	unconstrained · MANE · 5,150 bp · p 0.0024 · regional, not allelic
Overall
CADD	17.27	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.000678% European (non-Finnish) · 8/1,179,990 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,946 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.Asp9Glu
Coding: c.27C>A
MANE Select: NM_006736
Type: single nucleotide variant
Location: chr2:219279860 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.73 · 1 PDB
Residue 9: the j domain; a β-strand

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

Similar variants

DNAJB2 p.Asp9= Likely benign ★ same residue
DNAJB2 p.Arg178His Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Arg191Trp Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Asp248Asn Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Asp66Asn Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Gln224Pro Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Pro225Leu Uncertain significance ★★ ⚠ same condition
DNAJB2 p.Ser152Cys 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-asp9glu (accessed [today's date]).

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