Is BAG3 p.His166= (c.498C>T) pathogenic?

BAG3 p.His166= (c.498C>T) is classified Benign/Likely benign in BAG3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-03-27). Rare (popmax 0.113%, afr); Associated with Cardiovascular phenotype.

What condition is associated with BAG3 p.His166= (c.498C>T)?

BAG3 p.His166= (c.498C>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 6, dilated cardiomyopathy 1HH (ClinVar).

How common is BAG3 p.His166= (c.498C>T) in the general population?

BAG3 p.His166= (c.498C>T) is rare (popmax 0.113%, afr) (gnomAD).

BAG3 p.His166=

c.498C>T · rs111682654 · VCV389951

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.113%, afr)

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 -3.4	GERP -4.6
Overall
CADD	2.984	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.113% African / African-American · 85/75,050 alleles

Filtering AF 0.0938% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0866%

Overall 0.00975% 157/1,609,460 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.113%	883
Remaining individualsnot grpmax-eligible	0.0625%	1,599
Middle Eastern	0.0336%	2,975
Admixed American	0.00333%	29,990
South Asian	0.0033%	30,296
European (non-Finnish)	0.0022%	45,352

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.His166=
Coding: c.498C>T
MANE Select: NM_004281
dbSNP: rs111682654
Type: single nucleotide variant
Location: chr10:119670168 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 166: 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.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
BAG3 p.Gln244Ter 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-his166 (accessed [today's date]).

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