Is BAG3 p.Ala156Val (c.467C>T) pathogenic?

BAG3 p.Ala156Val (c.467C>T) is classified Conflicting classifications of pathogenicity in BAG3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-10). AlphaMissense: likely benign (0.0942); Very rare (popmax 0.00769%, sas); Associated with dilated cardiomyopathy 1HH.

What condition is associated with BAG3 p.Ala156Val (c.467C>T)?

BAG3 p.Ala156Val (c.467C>T) is associated with dilated cardiomyopathy 1HH, myofibrillar myopathy 6 (ClinVar).

How common is BAG3 p.Ala156Val (c.467C>T) in the general population?

BAG3 p.Ala156Val (c.467C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

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

What do computational predictors say about BAG3 p.Ala156Val (c.467C>T)?

AlphaMissense predicts likely benign (score 0.0942) — an in-silico prediction, not a clinical call.

BAG3 p.Ala156Val

c.467C>T · rs572038196 · VCV662194

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dilated cardiomyopathy 1HH

Computational evidence

Protein change
AlphaMissense	0.0942	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -8.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 1.1, phastCons 0.99
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic
Overall
CADD	19.23	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 0.00769% South Asian · 7/91,008 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00137% 22/1,610,440 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,001
African / African-American	0.00534%	18,728
Admixed American	0.005%	19,992
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,568
East Asian	0.00223%	44,872
Remaining individualsnot grpmax-eligible	0.0016%	62,356
Finnishnot grpmax-eligible	0.00159%	63,034
European (non-Finnish)	0.00034%	294,436

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.Ala156Val
Coding: c.467C>T
MANE Select: NM_004281
dbSNP: rs572038196
Type: single nucleotide variant
Location: chr10:119670137 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 156: 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.Ala156= Likely benign ★★ same residue
BAG3 p.Ala156Glu Uncertain significance ★ ⚠ same residue
BAG3 p.Ala156Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BAG3 p.Ala156Thr 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

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-ala156val (accessed [today's date]).

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