Is BAG3 p.Pro330= (c.990A>G) pathogenic?

BAG3 p.Pro330= (c.990A>G) is classified Likely benign in BAG3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). Very rare (popmax 8.47e-05%, nfe); Associated with dilated cardiomyopathy 1HH.

What condition is associated with BAG3 p.Pro330= (c.990A>G)?

BAG3 p.Pro330= (c.990A>G) is associated with dilated cardiomyopathy 1HH, myofibrillar myopathy 6 (ClinVar).

How common is BAG3 p.Pro330= (c.990A>G) in the general population?

BAG3 p.Pro330= (c.990A>G) is very rare (popmax 8.47e-05%, nfe) (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.Pro330=

c.990A>G · VCV3753098

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.12	GERP -0.88, phastCons 0.097
Overall
CADD	7.319	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,016 alleles

Overall 0.000658% 1/152,058 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: BAG3
Protein: p.Pro330=
Coding: c.990A>G
MANE Select: NM_004281
Type: single nucleotide variant
Location: chr10:119676544 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 330: 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.Pro330Leu Uncertain significance ★ ⚠ same residue
BAG3 p.Pro330Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
BAG3 p.Arg121Ter Pathogenic/Likely pathogenic ★★ same condition
BAG3 p.Arg123Ter Pathogenic/Likely pathogenic ★★ same condition
BAG3 p.Arg309Ter Pathogenic ★★ same condition
BAG3 p.Arg473Ter Pathogenic/Likely pathogenic ★★ same condition
BAG3 p.Arg90Ter Pathogenic ★★ same condition
BAG3 p.Gln132Ter 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/bag3-p-pro330 (accessed [today's date]).

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