Is MYBPC3 p.Arg44= (c.132C>T) pathogenic?

MYBPC3 p.Arg44= (c.132C>T) is classified Conflicting classifications of pathogenicity in MYBPC3 (ClinVar, Conflicting submitters, 15 submitters; last evaluated 2026-07-01). Rare (popmax 0.165%, mid); Associated with left ventricular noncompaction 10.

What condition is associated with MYBPC3 p.Arg44= (c.132C>T)?

MYBPC3 p.Arg44= (c.132C>T) is associated with left ventricular noncompaction 10, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is MYBPC3 p.Arg44= (c.132C>T) in the general population?

MYBPC3 p.Arg44= (c.132C>T) is rare (popmax 0.165%, mid) (gnomAD).

How is Left ventricular noncompaction inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MYBPC3 p.Arg44=

c.132C>T · rs377579620 · VCV42524

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 15 submitters

gnomAD v4.1

Rare

rare (popmax 0.165%, mid)

Conditions

left ventricular noncompaction 10

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 -1.8	GERP -3.7
Overall
CADD	1.649	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.165% Middle Eastern · 10/6,058 alleles

Filtering AF 0.0895% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0681%

Overall 0.00857% 138/1,609,520 alleles · rare exomes 127/1,457,154 · genomes 11/152,366 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.165%	606
East Asian	0.0268%	3,726
South Asian	0.0155%	6,459
Remaining individualsnot grpmax-eligible	0.0128%	7,791
European (non-Finnish)	0.00772%	12,951
Admixed American	0.00335%	29,842
Finnishnot grpmax-eligible	0.0016%	62,434

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.Arg44=
Coding: c.132C>T
MANE Select: NM_000256
dbSNP: rs377579620
Type: single nucleotide variant
Location: chr11:47351399 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.43 · 17 PDB

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

Disease context

left ventricular noncompaction 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy hypertrophic cardiomyopathy hypertrophic cardiomyopathy 4

For Left ventricular noncompaction (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages

Similar variants

MYBPC3 p.Arg44Cys Uncertain significance ★★ ⚠ same residue
MYBPC3 p.Arg44His 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-arg44 (accessed [today's date]).

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