MYBPC3 p.Asp228=
c.684T>C · rs532498780 · VCV1755790
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00266%, afr)
Conditions
1
hypertrophic cardiomyopathy
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 -2.5 | GERP -4.6 |
| Overall | ||
| CADD | 0.538 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00266%
African / African-American · 2/75,048 alleles
Filtering AF
0.000442%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000186%
3/1,613,396 alleles · very rare
exomes 1/1,461,094 · genomes 2/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00266% | 37,524 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,462 |
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
- MYBPC3
- Protein
- p.Asp228=
- Coding
- c.684T>C
- MANE Select
- NM_000256
- dbSNP
- rs532498780
- Type
- single nucleotide variant
- Location
- chr11:47348512 (GRCh38)
- Gene constraint
- LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.43 · 17 PDB
- Residue 228
- the ig-like c2-type 1 domain; a UniProt-annotated variant site (in cmh4)
Similar variants
- MYBPC3 p.Asp228Asn Uncertain significance ★★ ⚠ same residue
- MYBPC3 p.Asp228Gly Uncertain significance ★★ ⚠ same residue
- MYBPC3 p.Asp228Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
- MYBPC3 p.Asp228fs Pathogenic ★ same residue
- MYBPC3 p.Arg495Gln Likely pathogenic ★★★ ⚠ same condition
- MYBPC3 p.Arg495Gly Likely pathogenic ★★★ ⚠ same condition
- MYBPC3 p.Arg495Trp Likely pathogenic ★★★ ⚠ same condition
- MYBPC3 p.Arg502Gln 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/mybpc3-p-asp228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown