Is DNAJB2 c.229+2T>A pathogenic?

DNAJB2 c.229+2T>A is classified Pathogenic in DNAJB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-25). Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with DNAJB2 c.229+2T>A?

DNAJB2 c.229+2T>A is associated with Inborn genetic diseases (ClinVar).

How common is DNAJB2 c.229+2T>A in the general population?

DNAJB2 c.229+2T>A is very rare (popmax 0.00134%, afr) (gnomAD).

DNAJB2 c.229+2T>A

rs753570551 · VCV1789094

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ1.00	donor loss · deltas
Pangolin	Δ0.87	loss · gain 0.68 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.8	GERP 2.2, phastCons 1
Non-coding constraint	Z 3.67	1 kb window · o/e 0.73 · regional · uncalibrated
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,858 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000684% 10/1,461,744 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,858
European (non-Finnish)	0.000763%	131,097

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
Coding: c.229+2T>A
MANE Select: NM_006736
dbSNP: rs753570551
Type: single nucleotide variant
Location: chr2:219281773 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.73 · 1 PDB

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.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
DNAJB2 p.Ser170Phe 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-c-229-plus-2t-a (accessed [today's date]).

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