Is MSN p.Arg293Cys (c.877C>T) pathogenic?

MSN p.Arg293Cys (c.877C>T) is classified Uncertain significance in MSN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-29). AlphaMissense: likely pathogenic (0.9775); Absent from gnomAD v4.1; Associated with combined immunodeficiency due to moesin deficiency.

What condition is associated with MSN p.Arg293Cys (c.877C>T)?

MSN p.Arg293Cys (c.877C>T) is associated with combined immunodeficiency due to moesin deficiency (ClinVar).

How common is MSN p.Arg293Cys (c.877C>T) in the general population?

MSN p.Arg293Cys (c.877C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MSN p.Arg293Cys (c.877C>T)?

AlphaMissense predicts likely pathogenic (score 0.9775) — an in-silico prediction, not a clinical call.

MSN p.Arg293Cys

Q: How is Combined immunodeficiency due to Moesin deficiency inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.877C>T · rs1379781650 · VCV2584545

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9775 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined immunodeficiency due to moesin deficiency

Computational evidence

Protein change
AlphaMissense	0.9775	likely pathogenic
REVEL	0.762	pathogenic-leaning
SaProt	LLR -16.03	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.94, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 4,904 bp · p 5.1e-06 · regional, not allelic
Overall
CADD	32.0	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: MSN
Protein: p.Arg293Cys
Coding: c.877C>T
MANE Select: NM_002444
dbSNP: rs1379781650
Type: single nucleotide variant
Location: chrX:65735348 (GRCh38)
Structure: AlphaFold pLDDT 86.77 · 10 PDB
Residue 293: the ferm domain; an α-helix

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

Disease context

combined immunodeficiency due to moesin deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to Moesin deficiency (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood

Similar variants

MSN p.Arg171Trp Pathogenic ★★ same condition
MSN p.Arg273Trp Uncertain significance ★★ ⚠ same condition
MSN p.Glu367Lys Uncertain significance ★★ ⚠ same condition
MSN p.Arg553Ter Likely pathogenic ★ same condition
MSN p.Asp534Ala Likely pathogenic ★ same condition
MSN p.Arg381Cys Uncertain significance ★ ⚠ same condition
MSN p.Lys352fs Pathogenic same condition
MSN p.Ala122Thr Uncertain significance ★★ ⚠ same type

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/msn-p-arg293cys (accessed [today's date]).

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