Is MYBPC1 p.Leu796Pro (c.2387T>C) pathogenic?

MYBPC1 p.Leu796Pro (c.2387T>C) is classified Uncertain significance in MYBPC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-01). AlphaMissense: likely pathogenic (0.6188); Very rare (popmax 0.0011%, sas).

How common is MYBPC1 p.Leu796Pro (c.2387T>C) in the general population?

MYBPC1 p.Leu796Pro (c.2387T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about MYBPC1 p.Leu796Pro (c.2387T>C)?

AlphaMissense predicts likely pathogenic (score 0.6188) — an in-silico prediction, not a clinical call.

MYBPC1 p.Leu796Pro

c.2387T>C · VCV4918171

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6188 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6188	likely pathogenic
REVEL	0.197	benign-leaning
SaProt	LLR -7.85	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 53 kb · p 6e-11 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L789P vs ClinVar L796P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Overall 0.000124% 2/1,614,216 alleles · very rare exomes 2/1,461,884 · genomes 0/152,332 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,084
European (non-Finnish)	8.47e-05%	1,180,040

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: MYBPC1
Protein: p.Leu796Pro
Coding: c.2387T>C
MANE Select: NM_002465
Type: single nucleotide variant
Location: chr12:101667762 (GRCh38)
Gene constraint: LOEUF 0.433 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.99 · 8 PDB
Residue 789 UniProt numbering: the fibronectin type-iii 2 domain

Full MYBPC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MYBPC1 p.Arg265Gly Likely pathogenic ★★ ⚠ same type
MYBPC1 p.Glu248Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
MYBPC1 p.Leu259Pro Pathogenic/Likely pathogenic ★★ same type
MYBPC1 p.Leu263Arg Pathogenic ★★ same type
MYBPC1 p.Ala582Asp Uncertain significance ★★ ⚠ same type
MYBPC1 p.Ala73Thr Uncertain significance ★★ ⚠ same type
MYBPC1 p.Ala968Pro Uncertain significance ★★ ⚠ same type
MYBPC1 p.Arg146Gln Uncertain significance ★★ ⚠ same type

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/mybpc1-p-leu796pro (accessed [today's date]).

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