Is MYBPC3 p.Pro645= (c.1935C>G) pathogenic?

MYBPC3 p.Pro645= (c.1935C>G) is classified Likely benign in MYBPC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-27). Absent from gnomAD v4.1; Associated with hypertrophic cardiomyopathy.

What condition is associated with MYBPC3 p.Pro645= (c.1935C>G)?

MYBPC3 p.Pro645= (c.1935C>G) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is MYBPC3 p.Pro645= (c.1935C>G) in the general population?

MYBPC3 p.Pro645= (c.1935C>G) is absent from gnomAD v4.1 (gnomAD).

MYBPC3 p.Pro645=

c.1935C>G · rs727503193 · VCV1110796

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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 3.9	GERP -3.8, phastCons 1
Overall
CADD	8.839	PHRED · no single calibrated threshold — expert panels disagree

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.Pro645=
Coding: c.1935C>G
MANE Select: NM_000256
dbSNP: rs727503193
Type: single nucleotide variant
Location: chr11:47339783 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.43 · 17 PDB
Residue 645: the ig-like c2-type 5 domain

Full MYBPC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypertrophic cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYBPC3 p.Pro645Leu Conflicting classifications of pathogenicity ★ same residue
MYBPC3 p.Pro645Ser Uncertain significance ★ 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

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-pro645 (accessed [today's date]).

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