Is MSN p.Ala382= (c.1146C>G) pathogenic?

MSN p.Ala382= (c.1146C>G) is classified Benign/Likely benign in MSN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Rare (popmax 0.443%, afr).

How common is MSN p.Ala382= (c.1146C>G) in the general population?

MSN p.Ala382= (c.1146C>G) is rare (popmax 0.443%, afr) (gnomAD).

MSN p.Ala382=

c.1146C>G · rs149215829 · VCV1169552

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.443%, afr)

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 -1.1	GERP -3.7, phastCons 0.001
Overall
CADD	9.684	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.443% African / African-American · 253/57,095 alleles

Filtering AF 0.398% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.381%

Overall 0.032% 386/1,207,493 alleles · rare exomes 218/1,096,007 · genomes 168/111,486 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.443%	226
Admixed American	0.116%	859
Remaining individualsnot grpmax-eligible	0.0863%	1,159
Middle Eastern	0.069%	1,449
Ashkenazi Jewishnot grpmax-eligible	0.0682%	1,466
European (non-Finnish)	0.00224%	44,707
South Asian	0.00178%	56,186

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.Ala382=
Coding: c.1146C>G
MANE Select: NM_002444
dbSNP: rs149215829
Type: single nucleotide variant
Location: chrX:65737233 (GRCh38)
Structure: AlphaFold pLDDT 86.77 · 10 PDB
Residue 382: the 'disordered' region

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-ala382 (accessed [today's date]).

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