Is DNAJB6 p.Ala52= (c.156A>G) pathogenic?

DNAJB6 p.Ala52= (c.156A>G) is classified Likely benign in DNAJB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-06). Very rare (popmax 0.00267%, afr); Associated with autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6).

What condition is associated with DNAJB6 p.Ala52= (c.156A>G)?

DNAJB6 p.Ala52= (c.156A>G) is associated with autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (ClinVar).

How common is DNAJB6 p.Ala52= (c.156A>G) in the general population?

DNAJB6 p.Ala52= (c.156A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

How is DNAJB6-related limb-girdle muscular dystrophy D1 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

DNAJB6 p.Ala52=

c.156A>G · rs201239906 · VCV1368168

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)

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
Constraint at this position
Conservation	phyloP -10	GERP -4.1
Overall
CADD	0.221	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/75,016 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,610,398 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,508
European (non-Finnish)	8.49e-05%	1,178,207

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: DNAJB6
Protein: p.Ala52=
Coding: c.156A>G
MANE Select: NM_058246
dbSNP: rs201239906
Type: single nucleotide variant
Location: chr7:157363251 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.04 · 4 PDB
Residue 52: the j domain; an α-helix; the 'interaction with hsp70' region

Full DNAJB6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For DNAJB6-related limb-girdle muscular dystrophy D1 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

DNAJB6 p.Phe89Ile Pathogenic ★★ same condition
DNAJB6 p.Phe91Leu Pathogenic ★★ same condition
DNAJB6 p.Phe91Val Pathogenic/Likely pathogenic ★★ same condition
DNAJB6 p.Pro96Arg Pathogenic ★★ same condition
DNAJB6 c.66-2A>G Uncertain significance ★★ same condition
DNAJB6 c.-7G>A Uncertain significance ★★ same condition
DNAJB6 p.Ala22Val Uncertain significance ★★ ⚠ same condition
DNAJB6 p.Ala237Pro 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/dnajb6-p-ala52 (accessed [today's date]).

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