Is MSN p.Arg342Gln (c.1025G>A) pathogenic?

MSN p.Arg342Gln (c.1025G>A) is classified Uncertain significance in MSN (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-23). AlphaMissense: likely benign (0.0886); Very rare (popmax 0.00185%, sas).

How common is MSN p.Arg342Gln (c.1025G>A) in the general population?

MSN p.Arg342Gln (c.1025G>A) is very rare (popmax 0.00185%, sas) (gnomAD).

What do computational predictors say about MSN p.Arg342Gln (c.1025G>A)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

MSN p.Arg342Gln

c.1025G>A · VCV4688940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00185%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.281	benign-leaning
SaProt	LLR -7.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 4,904 bp · p 5.1e-06 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00185% South Asian · 1/53,955 alleles

Overall 0.000253% 3/1,184,053 alleles · very rare exomes 3/1,070,466 · genomes 0/113,587 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00185%	53,955
African / African-American	0.00175%	57,171
European (non-Finnish)	0.000114%	880,235

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: MSN
Protein: p.Arg342Gln
Coding: c.1025G>A
MANE Select: NM_002444
Type: single nucleotide variant
Location: chrX:65736860 (GRCh38)
Structure: AlphaFold pLDDT 86.77 · 10 PDB
Residue 342: the 'disordered' region; an α-helix

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

Similar variants

MSN p.Arg171Trp Pathogenic ★★ same type
MSN p.Ala122Thr Uncertain significance ★★ ⚠ same type
MSN p.Arg273Trp Uncertain significance ★★ ⚠ same type
MSN p.Arg293Cys Uncertain significance ★★ ⚠ same type
MSN p.Arg294Cys Uncertain significance ★★ ⚠ same type
MSN p.Arg295His Uncertain significance ★★ ⚠ same type
MSN p.Arg393His Uncertain significance ★★ ⚠ same type
MSN p.Glu346Asp 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-arg342gln (accessed [today's date]).

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