Is BAG3 p.Arg45Cys (c.133C>T) pathogenic?

BAG3 p.Arg45Cys (c.133C>T) is classified Conflicting classifications of pathogenicity in BAG3 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-19). AlphaMissense: likely pathogenic (0.822); Very rare (popmax 0.00545%, afr); Associated with Cardiovascular phenotype.

What condition is associated with BAG3 p.Arg45Cys (c.133C>T)?

BAG3 p.Arg45Cys (c.133C>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 6, dilated cardiomyopathy 1HH (ClinVar).

How common is BAG3 p.Arg45Cys (c.133C>T) in the general population?

BAG3 p.Arg45Cys (c.133C>T) is very rare (popmax 0.00545%, afr) (gnomAD).

What do computational predictors say about BAG3 p.Arg45Cys (c.133C>T)?

AlphaMissense predicts likely pathogenic (score 0.822) — an in-silico prediction, not a clinical call.

BAG3 p.Arg45Cys

c.133C>T · rs747820097 · VCV410233

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.822 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00545%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.822	likely pathogenic
REVEL	0.87	moderately pathogenic-leaning
SaProt	LLR -13.20	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.97, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00545% African / African-American · 4/73,458 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.0015% 24/1,597,936 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00545%	18,364
Remaining individualsnot grpmax-eligible	0.00162%	61,762
Finnishnot grpmax-eligible	0.00159%	62,784
European (non-Finnish)	0.00153%	65,167

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.Arg45Cys
Coding: c.133C>T
MANE Select: NM_004281
dbSNP: rs747820097
Type: single nucleotide variant
Location: chr10:119651808 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 45: the ww 1 domain; the 'disordered' region

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myofibrillar myopathy 6 dilated cardiomyopathy 1HH

Similar variants

BAG3 p.Arg45Gly Uncertain significance ★ ⚠ same residue
BAG3 p.Arg45Ser Uncertain significance ★ ⚠ 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-arg45cys (accessed [today's date]).

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