Is MSN p.Ala282= (c.846C>T) pathogenic?

MSN p.Ala282= (c.846C>T) is classified Likely benign in MSN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-02). Ultra-rare (popmax 0.0481%, mid).

How common is MSN p.Ala282= (c.846C>T) in the general population?

MSN p.Ala282= (c.846C>T) is ultra-rare (popmax 0.0481%, mid) (gnomAD).

MSN p.Ala282=

c.846C>T · rs2523012753 · VCV2700427

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0481%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -3.7
Overall
CADD	8.086	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0481% Middle Eastern · 2/4,156 alleles

Filtering AF 0.00848% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.000182% 2/1,096,839 alleles · ultra-rare

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.Ala282=
Coding: c.846C>T
MANE Select: NM_002444
dbSNP: rs2523012753
Type: single nucleotide variant
Location: chrX:65735317 (GRCh38)
Structure: AlphaFold pLDDT 86.77 · 10 PDB
Residue 282: the ferm domain; an α-helix

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

Similar variants

MSN p.Ala282Val Uncertain significance ★ ⚠ same residue
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

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-ala282 (accessed [today's date]).

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