Is MYBPC3 p.Arg306Gln (c.917G>A) pathogenic?

MYBPC3 p.Arg306Gln (c.917G>A) is classified Conflicting classifications of pathogenicity in MYBPC3 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-11-06). AlphaMissense: likely benign (0.1468); Ultra-rare (popmax 0.0173%, mid); Associated with Cardiovascular phenotype.

What condition is associated with MYBPC3 p.Arg306Gln (c.917G>A)?

MYBPC3 p.Arg306Gln (c.917G>A) is associated with Cardiovascular phenotype, cardiomyopathy, hypertrophic cardiomyopathy (ClinVar).

How common is MYBPC3 p.Arg306Gln (c.917G>A) in the general population?

MYBPC3 p.Arg306Gln (c.917G>A) is ultra-rare (popmax 0.0173%, mid) (gnomAD).

What do computational predictors say about MYBPC3 p.Arg306Gln (c.917G>A)?

AlphaMissense predicts likely benign (score 0.1468) — an in-silico prediction, not a clinical call.

MYBPC3 p.Arg306Gln

c.917G>A · rs373204728 · VCV42802

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1468 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1468	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	—	withheld · numbering disagrees past residue 302 · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 21 kb · p 0.0018 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% Middle Eastern · 1/5,786 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000824%

Overall 0.00169% 26/1,534,606 alleles · ultra-rare exomes 24/1,390,304 · genomes 2/144,302 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0173%	5,786
African / African-American	0.00429%	23,284
East Asian	0.00231%	43,246
Admixed American	0.00187%	53,542
Finnishnot grpmax-eligible	0.00162%	61,662
European (non-Finnish)	0.0016%	62,574
South Asian	0.00115%	86,598

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.Arg306Gln
Coding: c.917G>A
MANE Select: NM_000256
dbSNP: rs373204728
Type: single nucleotide variant
Location: chr11:47346636 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy hypertrophic cardiomyopathy

Similar variants

MYBPC3 p.Arg306Trp Conflicting classifications of pathogenicity ★ 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-arg306gln (accessed [today's date]).

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