Is MYOT p.Val366= (c.1098G>T) pathogenic?

MYOT p.Val366= (c.1098G>T) is classified Likely benign in MYOT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). Very rare (popmax 8.49e-05%, nfe); Associated with myofibrillar myopathy 3.

What condition is associated with MYOT p.Val366= (c.1098G>T)?

MYOT p.Val366= (c.1098G>T) is associated with myofibrillar myopathy 3 (ClinVar).

How common is MYOT p.Val366= (c.1098G>T) in the general population?

MYOT p.Val366= (c.1098G>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

How is Distal myotilinopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

MYOT p.Val366=

c.1098G>T · VCV3729050

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

myofibrillar myopathy 3

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 2.9	GERP -1.5, phastCons 1
Overall
CADD	7.237	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,592 alleles

Overall 6.85e-05% 1/1,458,930 alleles · very rare

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: MYOT
Protein: p.Val366=
Coding: c.1098G>T
MANE Select: NM_006790
Type: single nucleotide variant
Location: chr5:137886121 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.17 · 2 PDB
Residue 366: the ig-like c2-type 2 domain; a β-strand; the 'necessary for interaction with acta1' region; the 'necessary for interaction with flnc' region

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

Disease context

myofibrillar myopathy 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Distal myotilinopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

MYOT p.Ser55Phe Pathogenic/Likely pathogenic ★★ ⚠ same condition
MYOT p.Ser60Cys Pathogenic ★★ ⚠ same condition
MYOT p.Ser60Phe Pathogenic/Likely pathogenic ★★ same condition
MYOT c.531+4G>C Uncertain significance ★★ same condition
MYOT p.Ala131Glu Uncertain significance ★★ ⚠ same condition
MYOT p.Ala137Thr Uncertain significance ★★ ⚠ same condition
MYOT p.Ala218Val Uncertain significance ★★ ⚠ same condition
MYOT p.Arg178Cys 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/myot-p-val366 (accessed [today's date]).

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