Is MYBPC3 p.Ser1024= (c.3072C>T) pathogenic?

MYBPC3 p.Ser1024= (c.3072C>T) is classified Likely benign in MYBPC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-02). Very rare (popmax 0.00167%, amr); Associated with Cardiovascular phenotype.

What condition is associated with MYBPC3 p.Ser1024= (c.3072C>T)?

MYBPC3 p.Ser1024= (c.3072C>T) is associated with Cardiovascular phenotype, hypertrophic cardiomyopathy (ClinVar).

How common is MYBPC3 p.Ser1024= (c.3072C>T) in the general population?

MYBPC3 p.Ser1024= (c.3072C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

MYBPC3 p.Ser1024=

c.3072C>T · VCV3387099

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 4.9	GERP 1.7, phastCons 1
Overall
CADD	10.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,010 alleles

Overall 0.000186% 3/1,611,344 alleles · very rare exomes 3/1,458,980 · genomes 0/152,364 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,010
Finnishnot grpmax-eligible	0.00163%	61,510
European (non-Finnish)	8.48e-05%	1,179,786

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.Ser1024=
Coding: c.3072C>T
MANE Select: NM_000256
Type: single nucleotide variant
Location: chr11:47333675 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.43 · 17 PDB
Residue 1024: the ig-like c2-type 6 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: hypertrophic cardiomyopathy

Similar variants

MYBPC3 p.Ser1024Arg 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-ser1024 (accessed [today's date]).

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