Is MYBPC3 p.Pro147Ser (c.439C>T) pathogenic?

MYBPC3 p.Pro147Ser (c.439C>T) is classified Uncertain significance in MYBPC3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.1053); Very rare (popmax 0.00574%, amr); Associated with hypertrophic cardiomyopathy.

What condition is associated with MYBPC3 p.Pro147Ser (c.439C>T)?

MYBPC3 p.Pro147Ser (c.439C>T) is associated with hypertrophic cardiomyopathy, cardiomyopathy (ClinVar).

How common is MYBPC3 p.Pro147Ser (c.439C>T) in the general population?

MYBPC3 p.Pro147Ser (c.439C>T) is very rare (popmax 0.00574%, amr) (gnomAD).

What do computational predictors say about MYBPC3 p.Pro147Ser (c.439C>T)?

AlphaMissense predicts likely benign (score 0.1053) — an in-silico prediction, not a clinical call.

MYBPC3 p.Pro147Ser

c.439C>T · rs1204042102 · VCV845435

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1053 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00574%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.1053	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.34	GERP -0.12
Regional constraint	o/e 0.93	unconstrained · MANE · 21 kb · p 0.0018 · regional, not allelic
Overall
CADD	7.978	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00574% Admixed American · 3/52,276 alleles

Filtering AF 0.00152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000822%

Overall 0.000256% 4/1,560,676 alleles · very rare exomes 1/1,408,504 · genomes 3/152,172 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00574%	17,425
Ashkenazi Jewishnot grpmax-eligible	0.00348%	28,752

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.Pro147Ser
Coding: c.439C>T
MANE Select: NM_000256
dbSNP: rs1204042102
Type: single nucleotide variant
Location: chr11:47350080 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.43 · 17 PDB
Residue 147: the 'disordered' region; a UniProt-annotated variant site (in)

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

Disease context

hypertrophic cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy

Similar variants

MYBPC3 p.Pro147Leu Benign/Likely benign ★★ same residue
MYBPC3 p.Pro147fs 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

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-pro147ser (accessed [today's date]).

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