Is MSN p.Ser90= (c.270C>T) pathogenic?

MSN p.Ser90= (c.270C>T) is classified Likely benign in MSN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Very rare (popmax 0.00526%, afr).

How common is MSN p.Ser90= (c.270C>T) in the general population?

MSN p.Ser90= (c.270C>T) is very rare (popmax 0.00526%, afr) (gnomAD).

MSN p.Ser90=

c.270C>T · rs777718355 · VCV2193517

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00526%, 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 -3.6	GERP -3.7
Overall
CADD	1.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00526% African / African-American · 3/57,068 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000687%

Overall 0.000744% 9/1,209,734 alleles · very rare exomes 6/1,098,077 · genomes 3/111,657 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00526%	19,023
Finnishnot grpmax-eligible	0.00215%	46,535
European (non-Finnish)	0.000559%	179,042

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.Ser90=
Coding: c.270C>T
MANE Select: NM_002444
dbSNP: rs777718355
Type: single nucleotide variant
Location: chrX:65729515 (GRCh38)
Structure: AlphaFold pLDDT 86.77 · 10 PDB
Residue 90: the ferm domain; 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-ser90 (accessed [today's date]).

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