Is DNAJB6 p.Ser316= (c.948G>A) pathogenic?

DNAJB6 p.Ser316= (c.948G>A) is classified Benign/Likely benign in DNAJB6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-04). Rare (popmax 0.35%, sas); Associated with autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6).

What condition is associated with DNAJB6 p.Ser316= (c.948G>A)?

DNAJB6 p.Ser316= (c.948G>A) is associated with autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (ClinVar).

How common is DNAJB6 p.Ser316= (c.948G>A) in the general population?

DNAJB6 p.Ser316= (c.948G>A) is rare (popmax 0.35%, 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.

DNAJB6 p.Ser316=

c.948G>A · rs565527346 · VCV288447

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.35%, sas)

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 1.1	GERP -1.2, phastCons 1
Overall
CADD	11.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.35% South Asian · 319/91,070 alleles

Filtering AF 0.319% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.306%

Overall 0.0209% 337/1,613,898 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.35%	285
Remaining individualsnot grpmax-eligible	0.0224%	4,463
Middle Eastern	0.0165%	6,058
East Asian	0.00446%	22,438
European (non-Finnish)	8.48e-05%	1,179,832

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.Ser316=
Coding: c.948G>A
MANE Select: NM_058246
dbSNP: rs565527346
Type: single nucleotide variant
Location: chr7:157416065 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.04 · 4 PDB
Residue 316: the 'disordered' 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.Ser316Leu Uncertain significance ★★ ⚠ same residue
DNAJB6 p.Ser316Trp 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-ser316 (accessed [today's date]).

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