Is MYBPC3 p.Pro586fs (c.1755_1756del) pathogenic?

MYBPC3 p.Pro586fs (c.17551756del) is classified Pathogenic in MYBPC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-29). Associated with Cardiovascular phenotype.

What condition is associated with MYBPC3 p.Pro586fs (c.1755_1756del)?

MYBPC3 p.Pro586fs (c.1755_1756del) is associated with Cardiovascular phenotype (ClinVar).

MYBPC3 p.Pro586fs

c.1755_1756del · VCV3400413

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 18 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.6	GERP 1.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: MYBPC3
Protein: p.Pro586fs
Coding: c.1755_1756del
MANE Select: NM_000256
Type: Deletion
Location: chr11:47342025 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.43 · 17 PDB
Residue 586: the ig-like c2-type 4 domain

Full MYBPC3 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

Similar variants

MYBPC3 p.Pro586= Likely benign ★★ same residue
MYBPC3 c.1227-39_1263del Likely pathogenic ★★ same condition
MYBPC3 c.1404delG Pathogenic/Likely pathogenic ★★ same condition
MYBPC3 c.1792delG Pathogenic ★★ same condition
MYBPC3 c.1800delA Pathogenic ★★ same condition
MYBPC3 c.2291_2308+3del Likely pathogenic ★★ same condition
MYBPC3 c.2994+1del Likely pathogenic ★★ same condition
MYBPC3 c.3593_3627+20del Likely 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-pro586fs (accessed [today's date]).

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