Is DNAJB6 p.Phe93= (c.279C>T) pathogenic?

DNAJB6 p.Phe93= (c.279C>T) is classified Benign/Likely benign in DNAJB6 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-21). Rare (popmax 0.357%, nfe); Associated with autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6).

What condition is associated with DNAJB6 p.Phe93= (c.279C>T)?

DNAJB6 p.Phe93= (c.279C>T) is associated with autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (ClinVar).

How common is DNAJB6 p.Phe93= (c.279C>T) in the general population?

DNAJB6 p.Phe93= (c.279C>T) is rare (popmax 0.357%, nfe) (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.Phe93=

c.279C>T · rs149278319 · VCV281272

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.357%, nfe)

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 5.7	GERP 1.1, phastCons 1
Overall
CADD	12.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.357% European (non-Finnish) · 4,215/1,179,526 alleles

Filtering AF 0.348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.345%

Overall 0.281% 4,542/1,613,626 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.357%	280
Admixed American	0.195%	513
Remaining individualsnot grpmax-eligible	0.186%	539
Finnishnot grpmax-eligible	0.0687%	1,455
African / African-American	0.0586%	1,705
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
South Asian	0.0022%	45,535

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.Phe93=
Coding: c.279C>T
MANE Select: NM_058246
dbSNP: rs149278319
Type: single nucleotide variant
Location: chr7:157367416 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.04 · 4 PDB
Residue 93: a UniProt-annotated variant site (in lgmdd1; the mutation results in inefficient inhibition of protein aggregation by isoform b); 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.Phe93Leu Pathogenic ★ same residue
DNAJB6 p.Phe93fs Uncertain significance ★ same residue
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

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-phe93 (accessed [today's date]).

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