Is MYOM1 p.Val1663Met (c.4987G>A) pathogenic?

MYOM1 p.Val1663Met (c.4987G>A) is classified Conflicting classifications of pathogenicity in MYOM1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-06). AlphaMissense: likely pathogenic (0.8746); Ultra-rare (popmax 0.0216%, mid); Associated with non-immune hydrops fetalis.

What condition is associated with MYOM1 p.Val1663Met (c.4987G>A)?

MYOM1 p.Val1663Met (c.4987G>A) is associated with non-immune hydrops fetalis, hypertrophic cardiomyopathy (ClinVar).

How common is MYOM1 p.Val1663Met (c.4987G>A) in the general population?

MYOM1 p.Val1663Met (c.4987G>A) is ultra-rare (popmax 0.0216%, mid) (gnomAD).

What do computational predictors say about MYOM1 p.Val1663Met (c.4987G>A)?

AlphaMissense predicts likely pathogenic (score 0.8746) — an in-silico prediction, not a clinical call.

MYOM1 p.Val1663Met

c.4987G>A · rs751200138 · VCV190459

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8746 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0216%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

non-immune hydrops fetalis

Computational evidence

Protein change
AlphaMissense	0.8746	likely pathogenic
REVEL	0.85	moderately pathogenic-leaning
SaProt	LLR -12.08	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	27.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0216% Middle Eastern · 1/4,620 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000744% 12/1,611,966 alleles · ultra-rare exomes 11/1,459,736 · genomes 1/152,230 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0216%	4,620
East Asian	0.00446%	22,446
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
Admixed American	0.00167%	59,984
African / African-American	0.00134%	74,864
South Asian	0.0011%	90,972
European (non-Finnish)	0.000424%	235,964

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.Val1663Met
Coding: c.4987G>A
MANE Select: NM_003803
dbSNP: rs751200138
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

non-immune hydrops fetalis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy

Similar variants

MYOM1 p.Val1663Leu 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-val1663met (accessed [today's date]).

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