Is MYBPC3 p.Ser615= (c.1845C>T) pathogenic?

MYBPC3 p.Ser615= (c.1845C>T) is classified Likely benign in MYBPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-29). Very rare (popmax 8.56e-05%, nfe); Associated with hypertrophic cardiomyopathy.

What condition is associated with MYBPC3 p.Ser615= (c.1845C>T)?

MYBPC3 p.Ser615= (c.1845C>T) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is MYBPC3 p.Ser615= (c.1845C>T) in the general population?

MYBPC3 p.Ser615= (c.1845C>T) is very rare (popmax 8.56e-05%, nfe) (gnomAD).

MYBPC3 p.Ser615=

c.1845C>T · VCV3648149

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.56e-05%, nfe)

Conditions

hypertrophic cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.54 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP -0.069, phastCons 1
Overall
CADD	9.182	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.56e-05% European (non-Finnish) · 1/1,168,490 alleles

Overall 6.29e-05% 1/1,590,252 alleles · very rare exomes 1/1,438,002 · genomes 0/152,250 · joint denominator

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.Ser615=
Coding: c.1845C>T
MANE Select: NM_000256
Type: single nucleotide variant
Location: chr11:47341190 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.43 · 17 PDB
Residue 615: the ig-like c2-type 4 domain

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

Similar variants

MYBPC3 p.Ser615Gly Uncertain significance ★ same residue
MYBPC3 p.Ser615Arg 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-ser615 (accessed [today's date]).

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