Is MYBPC3 p.Ser85= (c.255C>T) pathogenic?

MYBPC3 p.Ser85= (c.255C>T) is classified Likely benign in MYBPC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-14). Very rare (popmax 0.0024%, eas); Associated with hypertrophic cardiomyopathy.

What condition is associated with MYBPC3 p.Ser85= (c.255C>T)?

MYBPC3 p.Ser85= (c.255C>T) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is MYBPC3 p.Ser85= (c.255C>T) in the general population?

MYBPC3 p.Ser85= (c.255C>T) is very rare (popmax 0.0024%, eas) (gnomAD).

MYBPC3 p.Ser85=

c.255C>T · rs1206735579 · VCV1098175

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0024%, eas)

Conditions

hypertrophic cardiomyopathy

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 2	GERP -1.5, phastCons 1
Overall
CADD	12.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0024% East Asian · 1/41,686 alleles

Overall 0.000129% 2/1,556,226 alleles · very rare exomes 1/1,403,986 · genomes 1/152,240 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0024%	41,686
European (non-Finnish)	8.72e-05%	1,146,434

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.Ser85=
Coding: c.255C>T
MANE Select: NM_000256
dbSNP: rs1206735579
Type: single nucleotide variant
Location: chr11:47351276 (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

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

Similar variants

MYBPC3 p.Ser85Phe Uncertain significance ★ same residue
MYBPC3 p.Ser85fs Pathogenic/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

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-ser85 (accessed [today's date]).

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