Is BAG3 p.Pro257= (c.771C>T) pathogenic?

BAG3 p.Pro257= (c.771C>T) is classified Conflicting classifications of pathogenicity in BAG3 (ClinVar, Conflicting submitters, 15 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0429%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with BAG3 p.Pro257= (c.771C>T)?

BAG3 p.Pro257= (c.771C>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 6, dilated cardiomyopathy 1HH (ClinVar).

How common is BAG3 p.Pro257= (c.771C>T) in the general population?

BAG3 p.Pro257= (c.771C>T) is ultra-rare (popmax 0.0429%, nfe) (gnomAD).

BAG3 p.Pro257=

c.771C>T · rs200212999 · VCV162778

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0429%, nfe)

Conditions

Cardiovascular phenotype

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 -0.49	GERP -1.8
Overall
CADD	9.396	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0429% European (non-Finnish) · 506/1,179,932 alleles

Filtering AF 0.0398% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0385%

Overall 0.0322% 519/1,614,034 alleles · ultra-rare exomes 479/1,461,704 · genomes 40/152,330 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0429%	2,332
Remaining individualsnot grpmax-eligible	0.0144%	6,944
African / African-American	0.00533%	18,765

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.Pro257=
Coding: c.771C>T
MANE Select: NM_004281
dbSNP: rs200212999
Type: single nucleotide variant
Location: chr10:119672518 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 257: 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.Pro257Ser Uncertain significance ★★ ⚠ same residue
BAG3 p.Pro257Arg Uncertain significance ★ ⚠ same residue
BAG3 p.Pro257Leu 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

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-pro257 (accessed [today's date]).

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