Is BAG3 p.Ile30Val (c.88A>G) pathogenic?

BAG3 p.Ile30Val (c.88A>G) is classified Uncertain significance in BAG3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-23). AlphaMissense: likely benign (0.0745); Very rare (popmax 0.00456%, eas); Associated with Cardiovascular phenotype.

What condition is associated with BAG3 p.Ile30Val (c.88A>G)?

BAG3 p.Ile30Val (c.88A>G) is associated with Cardiovascular phenotype, myofibrillar myopathy 6, dilated cardiomyopathy 1HH (ClinVar).

How common is BAG3 p.Ile30Val (c.88A>G) in the general population?

BAG3 p.Ile30Val (c.88A>G) is very rare (popmax 0.00456%, eas) (gnomAD).

What do computational predictors say about BAG3 p.Ile30Val (c.88A>G)?

AlphaMissense predicts likely benign (score 0.0745) — an in-silico prediction, not a clinical call.

BAG3 p.Ile30Val

c.88A>G · rs766796091 · VCV851274

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0745 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00456%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0745	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -8.06	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 1.6	GERP 0.64, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 26 kb · p 0.29 · regional, not allelic
Overall
CADD	19.36	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00456% East Asian · 2/43,848 alleles

Filtering AF 0.000756% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000476%

Overall 0.00106% 17/1,600,380 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00456%	21,924
Remaining individualsnot grpmax-eligible	0.00162%	61,874
African / African-American	0.00136%	73,722
European (non-Finnish)	0.00111%	90,307

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.Ile30Val
Coding: c.88A>G
MANE Select: NM_004281
dbSNP: rs766796091
Type: single nucleotide variant
Location: chr10:119651763 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.98
Residue 30: 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.Ile30Met 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
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-ile30val (accessed [today's date]).

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