Is MYBPC3 p.Pro656= (c.1968A>G) pathogenic?

MYBPC3 p.Pro656= (c.1968A>G) is classified Likely benign in MYBPC3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-25). Very rare (popmax 0.00801%, afr); Associated with Cardiovascular phenotype.

What condition is associated with MYBPC3 p.Pro656= (c.1968A>G)?

MYBPC3 p.Pro656= (c.1968A>G) is associated with Cardiovascular phenotype, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is MYBPC3 p.Pro656= (c.1968A>G) in the general population?

MYBPC3 p.Pro656= (c.1968A>G) is very rare (popmax 0.00801%, afr) (gnomAD).

MYBPC3 p.Pro656=

c.1968A>G · rs397515940 · VCV42589

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Conditions

Cardiovascular phenotype

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 -12	GERP -4.6
Overall
CADD	0.672	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,912 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000496% 8/1,613,814 alleles · very rare exomes 4/1,461,638 · genomes 4/152,176 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,485
Finnishnot grpmax-eligible	0.00312%	32,009

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.Pro656=
Coding: c.1968A>G
MANE Select: NM_000256
dbSNP: rs397515940
Type: single nucleotide variant
Location: chr11:47339750 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.43 · 17 PDB
Residue 656: the ig-like c2-type 5 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

Also linked: cardiomyopathy hypertrophic cardiomyopathy

Similar variants

MYBPC3 p.Pro656Ala Uncertain significance ★ ⚠ same residue
MYBPC3 p.Pro656Arg 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-pro656 (accessed [today's date]).

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