Is BAG3 p.Pro77= (c.231G>A) pathogenic?

BAG3 p.Pro77= (c.231G>A) is classified Benign/Likely benign in BAG3 (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.54%, afr); Associated with myofibrillar myopathy 6.

What condition is associated with BAG3 p.Pro77= (c.231G>A)?

BAG3 p.Pro77= (c.231G>A) is associated with myofibrillar myopathy 6, dilated cardiomyopathy 1HH (ClinVar).

How common is BAG3 p.Pro77= (c.231G>A) in the general population?

BAG3 p.Pro77= (c.231G>A) is low-frequency (popmax 1.54%, afr) (gnomAD).

How is BAG3-related myofibrillar myopathy inherited?

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

BAG3 p.Pro77=

c.231G>A · rs143752613 · VCV44781

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.54%, afr)

Conditions

myofibrillar myopathy 6

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 0.64	GERP -2.4, phastCons 0.82
Overall
CADD	2.404	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.54% African / African-American · 1,158/75,036 alleles

Filtering AF 1.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.44%

Overall 0.0853% 1,377/1,614,182 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.54%	65
Middle Eastern	0.181%	551
Remaining individualsnot grpmax-eligible	0.128%	781
Admixed American	0.0983%	1,017
East Asian	0.0111%	8,976
European (non-Finnish)	0.00525%	19,033
South Asian	0.0022%	45,540

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.Pro77=
Coding: c.231G>A
MANE Select: NM_004281
dbSNP: rs143752613
Type: single nucleotide variant
Location: chr10:119669901 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 77: a UniProt-annotated variant site (in); the 'disordered' region

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

Disease context

myofibrillar myopathy 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1HH

For BAG3-related myofibrillar myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Childhood

Similar variants

BAG3 p.Pro77Leu Benign/Likely benign ★★ 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
BAG3 p.Gln135Ter 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-pro77 (accessed [today's date]).

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