Is MYBPC3 p.Pro694= (c.2082A>G) pathogenic?

MYBPC3 p.Pro694= (c.2082A>G) is classified Likely benign in MYBPC3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-13). Very rare (popmax 0.00102%, nfe); Associated with cardiomyopathy.

What condition is associated with MYBPC3 p.Pro694= (c.2082A>G)?

MYBPC3 p.Pro694= (c.2082A>G) is associated with cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is MYBPC3 p.Pro694= (c.2082A>G) in the general population?

MYBPC3 p.Pro694= (c.2082A>G) is very rare (popmax 0.00102%, nfe) (gnomAD).

MYBPC3 p.Pro694=

c.2082A>G · rs756589409 · VCV1171401

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Conditions

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 -5.8	GERP -3.7
Overall
CADD	0.266	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,880 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000744% 12/1,613,912 alleles · very rare exomes 10/1,461,682 · genomes 2/152,230 · 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.Pro694=
Coding: c.2082A>G
MANE Select: NM_000256
dbSNP: rs756589409
Type: single nucleotide variant
Location: chr11:47339390 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.43 · 17 PDB
Residue 694: the ig-like c2-type 5 domain

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

Disease context

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

Also linked: hypertrophic cardiomyopathy

Similar variants

MYBPC3 p.Pro694Arg Uncertain significance ★★ ⚠ same residue
MYBPC3 p.Pro694Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro694 (accessed [today's date]).

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