MYBPC3 p.Phe448=
c.1344T>C · rs979655756 · VCV1646490
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00186%, nfe)
Conditions
3
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.21 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.3 | GERP -5 |
| Overall | ||
| CADD | 0.634 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00186%
European (non-Finnish) · 22/1,179,742 alleles
Filtering AF
0.00122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00136%
22/1,613,160 alleles · very rare
exomes 21/1,460,998 · genomes 1/152,162 · joint denominator
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.Phe448=
- Coding
- c.1344T>C
- MANE Select
- NM_000256
- dbSNP
- rs979655756
- Type
- single nucleotide variant
- Location
- chr11:47343028 (GRCh38)
- Gene constraint
- LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.43 · 17 PDB
- Residue 448
- a β-strand; the ig-like c2-type 2 domain
Similar variants
- MYBPC3 p.Phe448Ser Likely 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
- MYBPC3 c.26-2A>G Uncertain significance ★★★ same condition
- MYBPC3 p.Arg1271Ter Uncertain significance ★★★ same condition
- MYBPC3 p.Lys135= Uncertain significance ★★★ 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-phe448 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown