Is DNAJB6 p.Phe123del (c.363CTT[1]) pathogenic?

DNAJB6 p.Phe123del (c.363CTT[1]) is classified Uncertain significance in DNAJB6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-08). Very rare (popmax 0.00136%, afr); Associated with autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6).

What condition is associated with DNAJB6 p.Phe123del (c.363CTT[1])?

DNAJB6 p.Phe123del (c.363CTT[1]) is associated with autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (ClinVar).

How common is DNAJB6 p.Phe123del (c.363CTT[1]) in the general population?

DNAJB6 p.Phe123del (c.363CTT[1]) is very rare (popmax 0.00136%, 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.Phe123del

c.363CTT[1] · rs1563136940 · VCV595118

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00136%, 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 · substitutions only
Constraint at this position
Conservation	phyloP 6.8	GERP 2, phastCons 1
Overall
CADD	18.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% African / African-American · 1/73,754 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000312% 5/1,601,178 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00136%	73,754
South Asian	0.00113%	88,174
European (non-Finnish)	0.000255%	392,257

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.Phe123del
Coding: c.363CTT[1]
MANE Select: NM_058246
dbSNP: rs1563136940
Type: Microsatellite
Location: chr7:157382262 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.04 · 4 PDB
Residue 123: the 'interaction with hsp70' region; the 'interaction with krt18' 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.Glu280_Gly281insGluGlu Uncertain significance ★★ same condition
DNAJB6 p.Lys320del Uncertain significance ★★ same condition
DNAJB6 p.Asp98del Pathogenic ★ same condition
DNAJB6 p.Glu314fs Uncertain significance ★ same condition
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

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-phe123del (accessed [today's date]).

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