Is MYBPC3 p.Pro618= (c.1854C>T) pathogenic?

MYBPC3 p.Pro618= (c.1854C>T) is classified Likely benign in MYBPC3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-12). Very rare (popmax 0.00521%, amr); Associated with cardiomyopathy.

What condition is associated with MYBPC3 p.Pro618= (c.1854C>T)?

MYBPC3 p.Pro618= (c.1854C>T) is associated with cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is MYBPC3 p.Pro618= (c.1854C>T) in the general population?

MYBPC3 p.Pro618= (c.1854C>T) is very rare (popmax 0.00521%, amr) (gnomAD).

MYBPC3 p.Pro618=

c.1854C>T · rs1459242483 · VCV925421

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00521%, amr)

Conditions

cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -16	GERP -4.6
Overall
CADD	0.767	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00521% Admixed American · 3/57,544 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000684%

Overall 0.000627% 10/1,595,600 alleles · very rare exomes 7/1,443,608 · genomes 3/151,992 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00521%	19,181
African / African-American	0.00404%	24,782
Remaining individualsnot grpmax-eligible	0.00324%	30,869
South Asian	0.00114%	87,700
European (non-Finnish)	8.54e-05%	1,171,550

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.Pro618=
Coding: c.1854C>T
MANE Select: NM_000256
dbSNP: rs1459242483
Type: single nucleotide variant
Location: chr11:47341181 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.43 · 17 PDB
Residue 618: the ig-like c2-type 4 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.Pro618fs Likely pathogenic ★ 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-pro618 (accessed [today's date]).

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