Is MUSK p.Pro599Ser (c.1795C>T) pathogenic?

MUSK p.Pro599Ser (c.1795C>T) is classified Uncertain significance in MUSK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-31). AlphaMissense: ambiguous (0.3956); Absent from gnomAD v4.1; Associated with congenital myasthenic syndrome 9.

What condition is associated with MUSK p.Pro599Ser (c.1795C>T)?

MUSK p.Pro599Ser (c.1795C>T) is associated with congenital myasthenic syndrome 9, fetal akinesia deformation sequence 1 (ClinVar).

How common is MUSK p.Pro599Ser (c.1795C>T) in the general population?

MUSK p.Pro599Ser (c.1795C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MUSK p.Pro599Ser (c.1795C>T)?

AlphaMissense predicts ambiguous (score 0.3956) — an in-silico prediction, not a clinical call.

MUSK p.Pro599Ser

c.1795C>T · rs2077898173 · VCV948890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3956 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital myasthenic syndrome 9

Computational evidence

Protein change
AlphaMissense	0.3956	ambiguous
REVEL	0.334	indeterminate
SaProt	LLR -6.94	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 132 kb · p 0.07 · regional, not allelic
Overall
CADD	23.7	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

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: MUSK
Protein: p.Pro599Ser
Coding: c.1795C>T
MANE Select: NM_005592
dbSNP: rs2077898173
Type: single nucleotide variant
Location: chr9:110787706 (GRCh38)
Gene constraint: LOEUF 0.778 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.57 · 6 PDB
Residue 599: the protein kinase domain

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

Disease context

congenital myasthenic syndrome 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: fetal akinesia deformation sequence 1

Similar variants

MUSK c.1586+1G>A Likely pathogenic ★★ same condition
MUSK c.79+2T>G Pathogenic ★★ same condition
MUSK p.Arg264Ter Pathogenic ★★ same condition
MUSK p.Arg816Ter Pathogenic/Likely pathogenic ★★ same condition
MUSK p.Asp38Glu Likely pathogenic ★★ ⚠ same condition
MUSK p.Ile575Thr Pathogenic/Likely pathogenic ★★ same condition
MUSK p.Lys720Glu Likely pathogenic ★★ ⚠ same condition
MUSK p.Met1Thr Pathogenic ★★ 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/musk-p-pro599ser (accessed [today's date]).

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