Is MYOM1 p.Arg464= (c.1392G>A) pathogenic?

MYOM1 p.Arg464= (c.1392G>A) is classified Benign/Likely benign in MYOM1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 26.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hypertrophic cardiomyopathy.

What condition is associated with MYOM1 p.Arg464= (c.1392G>A)?

MYOM1 p.Arg464= (c.1392G>A) is associated with hypertrophic cardiomyopathy (ClinVar).

MYOM1 p.Arg464=

Q: How common is MYOM1 p.Arg464= (c.1392G>A) in the general population?

MYOM1 p.Arg464= (c.1392G>A) is common (popmax 26.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1392G>A · rs11659820 · VCV226800

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 26.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hypertrophic cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.75	GERP -0.15, phastCons 1
Overall
CADD	8.764	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 26.8% African / African-American · 20,105/74,948 alleles

Filtering AF 26.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.4%

Overall 20.4% 328,806/1,609,800 alleles · common exomes 296,877/1,457,598 · genomes 31,929/152,202 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	28.6%	3
African / African-Americangrpmax	26.8%	4
European (non-Finnish)	21.6%	5
Middle Eastern	21.3%	5
Remaining individualsnot grpmax-eligible	19.3%	5
Ashkenazi Jewishnot grpmax-eligible	19.2%	5
South Asian	17.9%	6
Admixed American	16.6%	6
Finnishnot grpmax-eligible	14.7%	7
East Asian	0.457%	219

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MYOM1
Protein: p.Arg464=
Coding: c.1392G>A
MANE Select: NM_003803
dbSNP: rs11659820
Type: single nucleotide variant
Location: chr18:3164387 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.52 · 9 PDB
Residue 464: the ig-like c2-type 2 domain

Full MYOM1 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

MYOM1 p.Arg464Gln Uncertain significance ★★ ⚠ same residue
MYOM1 p.Arg464Trp Uncertain significance ★ same residue
MYOM1 c.1111+4G>T Uncertain significance ★★ same condition
MYOM1 p.Ala1021Val Uncertain significance ★★ ⚠ same condition
MYOM1 p.Ala1024Thr Uncertain significance ★★ ⚠ same condition
MYOM1 p.Ala1037Thr Uncertain significance ★★ ⚠ same condition
MYOM1 p.Ala1082Gly Uncertain significance ★★ ⚠ same condition
MYOM1 p.Ala1093Val 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/myom1-p-arg464 (accessed [today's date]).

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