Is MYBPC3 p.Phe90= (c.270C>T) pathogenic?

MYBPC3 p.Phe90= (c.270C>T) is classified Likely benign in MYBPC3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-02). Ultra-rare (popmax 0.0109%, afr); Associated with Cardiovascular phenotype.

What condition is associated with MYBPC3 p.Phe90= (c.270C>T)?

MYBPC3 p.Phe90= (c.270C>T) is associated with Cardiovascular phenotype, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is MYBPC3 p.Phe90= (c.270C>T) in the general population?

MYBPC3 p.Phe90= (c.270C>T) is ultra-rare (popmax 0.0109%, afr) (gnomAD).

MYBPC3 p.Phe90=

c.270C>T · rs367990952 · VCV705515

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0109%, afr)

Conditions

Cardiovascular phenotype

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 1.2	GERP -2.4, phastCons 1
Overall
CADD	10.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0109% African / African-American · 8/73,308 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00388%

Overall 0.0031% 48/1,548,184 alleles · ultra-rare exomes 42/1,395,992 · genomes 6/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0109%	9,163
Remaining individualsnot grpmax-eligible	0.00334%	29,907
European (non-Finnish)	0.00316%	31,691
Admixed American	0.0019%	52,500
South Asian	0.00118%	84,492

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.Phe90=
Coding: c.270C>T
MANE Select: NM_000256
dbSNP: rs367990952
Type: single nucleotide variant
Location: chr11:47351261 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.43 · 17 PDB
Residue 90: a β-strand

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.Phe90Leu 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-phe90 (accessed [today's date]).

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