Is DNAJB6 p.Gln48Glu (c.142C>G) pathogenic?

DNAJB6 p.Gln48Glu (c.142C>G) is classified Uncertain significance in DNAJB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-04). AlphaMissense: likely benign (0.1019); Very rare (popmax 0.00333%, sas); Associated with autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6).

What condition is associated with DNAJB6 p.Gln48Glu (c.142C>G)?

DNAJB6 p.Gln48Glu (c.142C>G) is associated with autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (ClinVar).

How common is DNAJB6 p.Gln48Glu (c.142C>G) in the general population?

DNAJB6 p.Gln48Glu (c.142C>G) is very rare (popmax 0.00333%, sas) (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.

What do computational predictors say about DNAJB6 p.Gln48Glu (c.142C>G)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

DNAJB6 p.Gln48Glu

c.142C>G · rs1799691943 · VCV963673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -5.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.98 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.3	GERP 1, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 8,817 bp · p 0.017 · regional, not allelic
Overall
CADD	18.89	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 0.00333% South Asian · 3/90,136 alleles

Filtering AF 0.000884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000445%

Overall 0.000206% 3/1,458,910 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: DNAJB6
Protein: p.Gln48Glu
Coding: c.142C>G
MANE Select: NM_058246
dbSNP: rs1799691943
Type: single nucleotide variant
Location: chr7:157363237 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.04 · 4 PDB
Residue 48: 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-gln48glu (accessed [today's date]).

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