Is BAG3 p.Ser181Asn (c.541_542delinsAA) pathogenic?

BAG3 p.Ser181Asn (c.541542delinsAA) is classified Uncertain significance in BAG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-28). Absent from gnomAD; Associated with dilated cardiomyopathy 1HH.

What condition is associated with BAG3 p.Ser181Asn (c.541_542delinsAA)?

BAG3 p.Ser181Asn (c.541_542delinsAA) is associated with dilated cardiomyopathy 1HH, myofibrillar myopathy 6 (ClinVar).

How common is BAG3 p.Ser181Asn (c.541_542delinsAA) in the general population?

BAG3 p.Ser181Asn (c.541_542delinsAA) is absent from gnomAD (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

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

BAG3 p.Ser181Asn

c.541_542delinsAA · rs2494013458 · VCV2000097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

dilated cardiomyopathy 1HH

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 5	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BAG3
Protein: p.Ser181Asn
Coding: c.541_542delinsAA
MANE Select: NM_004281
dbSNP: rs2494013458
Type: Indel
Location: chr10:119672288 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 181: the 'disordered' region

Full BAG3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy 1HH — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myofibrillar myopathy 6

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

BAG3 p.Ser181Phe Uncertain significance ★★ ⚠ same residue
BAG3 p.Ser181= Likely benign ★ same residue
BAG3 p.Glu461Leu Uncertain significance ★★ same condition
BAG3 p.Val432Met Uncertain significance ★★ same condition
BAG3 c.910-21_910-20delinsCG Uncertain significance ★ same condition
BAG3 p.Leu465Met Uncertain significance ★ same condition
BAG3 p.Pro334Leu Uncertain significance ★ same condition
BAG3 p.Trp49Val 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/bag3-p-ser181asn (accessed [today's date]).

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