Is MYOM1 p.Pro1069= (c.3207G>A) pathogenic?

MYOM1 p.Pro1069= (c.3207G>A) is classified Benign/Likely benign in MYOM1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-21). Rare (popmax 0.228%, afr); Associated with hypertrophic cardiomyopathy.

What condition is associated with MYOM1 p.Pro1069= (c.3207G>A)?

MYOM1 p.Pro1069= (c.3207G>A) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is MYOM1 p.Pro1069= (c.3207G>A) in the general population?

MYOM1 p.Pro1069= (c.3207G>A) is rare (popmax 0.228%, afr) (gnomAD).

MYOM1 p.Pro1069=

c.3207G>A · rs367633441 · VCV416043

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.228%, afr)

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 -20	GERP -3.4
Overall
CADD	0.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.228% African / African-American · 171/74,916 alleles

Filtering AF 0.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.19%

Overall 0.0133% 214/1,613,588 alleles · rare exomes 126/1,461,432 · genomes 88/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.228%	438
Remaining individualsnot grpmax-eligible	0.0224%	4,461
Admixed American	0.0167%	5,996
Middle Eastern	0.0165%	6,062
South Asian	0.0033%	30,342
European (non-Finnish)	0.00127%	78,653

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.Pro1069=
Coding: c.3207G>A
MANE Select: NM_003803
dbSNP: rs367633441
Type: single nucleotide variant
Location: chr18:3116427 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.52 · 9 PDB
Residue 1069: the fibronectin type-iii 5 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.Pro1069Leu 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
MYOM1 p.Ala1094Pro 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-pro1069 (accessed [today's date]).

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