Is MYOM1 p.Val1663Leu (c.4987G>T) pathogenic?

MYOM1 p.Val1663Leu (c.4987G>T) is classified Uncertain significance in MYOM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-17). AlphaMissense: likely pathogenic (0.8089); Absent from gnomAD v4.1; Associated with hypertrophic cardiomyopathy.

What condition is associated with MYOM1 p.Val1663Leu (c.4987G>T)?

MYOM1 p.Val1663Leu (c.4987G>T) is associated with hypertrophic cardiomyopathy (ClinVar).

How common is MYOM1 p.Val1663Leu (c.4987G>T) in the general population?

MYOM1 p.Val1663Leu (c.4987G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MYOM1 p.Val1663Leu (c.4987G>T)?

AlphaMissense predicts likely pathogenic (score 0.8089) — an in-silico prediction, not a clinical call.

MYOM1 p.Val1663Leu

c.4987G>T · VCV4779701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8089 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypertrophic cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.8089	likely pathogenic
REVEL	0.794	moderately pathogenic-leaning
SaProt	LLR -12.53	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 148 kb · p 0.012 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MYOM1
Protein: p.Val1663Leu
Coding: c.4987G>T
MANE Select: NM_003803
Type: single nucleotide variant
Location: chr18:3067333 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.52 · 9 PDB
Residue 1663: a β-strand

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.Val1663Met Conflicting classifications of pathogenicity ★ ⚠ 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-val1663leu (accessed [today's date]).

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