Is MYBPC3 p.Pro778= (c.2334C>T) pathogenic?

MYBPC3 p.Pro778= (c.2334C>T) is classified Likely benign in MYBPC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-26). Very rare (popmax 0.00119%, sas); Associated with cardiomyopathy.

What condition is associated with MYBPC3 p.Pro778= (c.2334C>T)?

MYBPC3 p.Pro778= (c.2334C>T) is associated with cardiomyopathy (ClinVar).

How common is MYBPC3 p.Pro778= (c.2334C>T) in the general population?

MYBPC3 p.Pro778= (c.2334C>T) is very rare (popmax 0.00119%, sas) (gnomAD).

MYBPC3 p.Pro778=

c.2334C>T · rs2095884023 · VCV915580

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

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 -0.14	GERP -4.5
Overall
CADD	6.807	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% South Asian · 1/84,272 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000322% 5/1,552,958 alleles · very rare exomes 5/1,400,822 · genomes 0/152,136 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00119%	84,272
European (non-Finnish)	0.000348%	287,030

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.Pro778=
Coding: c.2334C>T
MANE Select: NM_000256
dbSNP: rs2095884023
Type: single nucleotide variant
Location: chr11:47337769 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.43 · 17 PDB
Residue 778: the fibronectin type-iii 1 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

Similar variants

MYBPC3 p.Pro778Leu 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
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-pro778 (accessed [today's date]).

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