Is MYBPC3 p.Pro150= (c.450C>T) pathogenic?

MYBPC3 p.Pro150= (c.450C>T) is classified Benign/Likely benign in MYBPC3 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0862%, eas); Associated with Cardiovascular phenotype.

What condition is associated with MYBPC3 p.Pro150= (c.450C>T)?

MYBPC3 p.Pro150= (c.450C>T) is associated with Cardiovascular phenotype, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is MYBPC3 p.Pro150= (c.450C>T) in the general population?

MYBPC3 p.Pro150= (c.450C>T) is ultra-rare (popmax 0.0862%, eas) (gnomAD).

MYBPC3 p.Pro150=

c.450C>T · rs377520770 · VCV42753

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0862%, eas)

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 -9.1	GERP -2.1
Overall
CADD	0.038	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0862% East Asian · 36/41,740 alleles

Filtering AF 0.0639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0563%

Overall 0.00858% 134/1,561,618 alleles · ultra-rare exomes 120/1,409,354 · genomes 14/152,264 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0862%	1,159
South Asian	0.0177%	5,647
African / African-American	0.0109%	9,200
Remaining individualsnot grpmax-eligible	0.00991%	10,088
European (non-Finnish)	0.0059%	16,949
Admixed American	0.00191%	52,446

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.Pro150=
Coding: c.450C>T
MANE Select: NM_000256
dbSNP: rs377520770
Type: single nucleotide variant
Location: chr11:47350069 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.43 · 17 PDB
Residue 150: the 'disordered' region

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.Pro150Leu 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-pro150 (accessed [today's date]).

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