BAG3 p.Asp518=
c.1554T>C · rs139125612 · VCV2191746
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
Conditions
3
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 -1.1 | GERP -4.9 |
| Overall | ||
| CADD | 1.379 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/59,992 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.000929%
15/1,614,008 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 5,999 |
| African / African-American | 0.00668% | 14,981 |
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.Asp518=
- Coding
- c.1554T>C
- MANE Select
- NM_004281
- dbSNP
- rs139125612
- Type
- single nucleotide variant
- Location
- chr10:119677108 (GRCh38)
- Gene constraint
- LOEUF 0.538 · pLI 0.92 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 57.98
Similar variants
- BAG3 p.Asp518Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
- BAG3 p.Asp518His 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-asp518 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown