MYBPC3 p.Ser593Pro
c.1777T>C · VCV3915215
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.8876 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8876 | likely pathogenic |
|---|---|---|
| REVEL | 0.324 | indeterminate |
| SaProt | — | withheld · numbering disagrees past residue 302 · why |
| Splicing | ||
| SpliceAI | Δ0.36 | donor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP 9.2 | GERP 2.2, phastCons 1 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 21 kb · p 0.0018 · regional, not allelic |
| Overall | ||
| CADD | 25.4 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- MYBPC3
- Protein
- p.Ser593Pro
- Coding
- c.1777T>C
- MANE Select
- NM_000256
- Type
- single nucleotide variant
- Location
- chr11:47342004 (GRCh38)
- Gene constraint
- LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 79.43 · 17 PDB
- Residue 593
- the ig-like c2-type 4 domain
Similar variants
- MYBPC3 p.Ser593Phe Uncertain significance ★★ same residue
- MYBPC3 p.Ser593fs Pathogenic ★★ same residue
- MYBPC3 c.1090+1G>A Pathogenic ★★ same condition
- MYBPC3 c.1091-2A>G Pathogenic/Likely pathogenic ★★ same condition
- MYBPC3 c.1224-2A>G Pathogenic/Likely pathogenic ★★ same condition
- MYBPC3 c.1224-80G>A Pathogenic/Likely pathogenic ★★ same condition
- MYBPC3 c.1227-2A>G Pathogenic/Likely pathogenic ★★ same condition
- MYBPC3 c.1351+1G>A 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-ser593pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown