Is DNAJB2 p.Ala52Thr (c.154G>A) pathogenic?

DNAJB2 p.Ala52Thr (c.154G>A) is classified Uncertain significance in DNAJB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-17). AlphaMissense: likely pathogenic (0.9953); Absent from gnomAD v4.1.

How common is DNAJB2 p.Ala52Thr (c.154G>A) in the general population?

DNAJB2 p.Ala52Thr (c.154G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DNAJB2 p.Ala52Thr (c.154G>A)?

AlphaMissense predicts likely pathogenic (score 0.9953) — an in-silico prediction, not a clinical call.

DNAJB2 p.Ala52Thr

c.154G>A · rs2545028265 · VCV1809642

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9953 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9953	likely pathogenic · top 4% in DNAJB2
REVEL	0.723	pathogenic-leaning
SaProt	LLR -15.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 5,150 bp · p 0.0024 · regional, not allelic
Overall
CADD	33.0	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

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.Ala52Thr
Coding: c.154G>A
MANE Select: NM_006736
dbSNP: rs2545028265
Type: single nucleotide variant
Location: chr2:219280666 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.73 · 1 PDB
Residue 52: the j domain; an α-helix

Full DNAJB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB2 p.Ala52= Likely benign ★ same residue
DNAJB2 c.175+2T>A Pathogenic/Likely pathogenic ★★ same type
DNAJB2 c.352+1G>A Pathogenic ★★ same type
DNAJB2 c.65+1G>A Likely pathogenic ★★ same type
DNAJB2 p.Arg104Gln Uncertain significance ★★ ⚠ same type
DNAJB2 p.Arg165Cys Uncertain significance ★★ ⚠ same type
DNAJB2 p.Arg178His Uncertain significance ★★ ⚠ same type
DNAJB2 p.Arg182Cys 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/dnajb2-p-ala52thr (accessed [today's date]).

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