Is DNAJB2 p.Ala22= (c.66G>T) pathogenic?

DNAJB2 p.Ala22= (c.66G>T) is classified Likely benign in DNAJB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DNAJB2 p.Ala22= (c.66G>T)?

DNAJB2 p.Ala22= (c.66G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DNAJB2 p.Ala22= (c.66G>T) in the general population?

DNAJB2 p.Ala22= (c.66G>T) is absent from gnomAD v4.1 (gnomAD).

DNAJB2 p.Ala22=

c.66G>T · VCV4617702

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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
Pangolin	Δ0.23	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3.6	GERP 0.86, phastCons 1
Overall
CADD	19.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DNAJB2
Protein: p.Ala22=
Coding: c.66G>T
MANE Select: NM_006736
Type: single nucleotide variant
Location: chr2:219280578 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.73 · 1 PDB
Residue 22: the j domain; an α-helix

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.Ala22Pro Uncertain significance ★ ⚠ same residue
DNAJB2 p.Ala22Glu Uncertain significance ★ ⚠ 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

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-ala22 (accessed [today's date]).

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