MSN p.Pro154=
c.462G>A · rs745873198 · VCV3015042
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.023%, 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 -2.1 | GERP -3.4 |
| Overall | ||
| CADD | 3.484 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.023%
Middle Eastern · 1/4,348 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00271%
Overall
0.00132%
16/1,207,568 alleles · ultra-rare
exomes 13/1,095,310 · genomes 3/112,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.023% | 4,348 |
| Admixed American | 0.0109% | 9,143 |
| African / African-American | 0.00699% | 14,308 |
| South Asian | 0.00355% | 28,176 |
| European (non-Finnish) | 0.000448% | 223,435 |
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.Pro154=
- Coding
- c.462G>A
- MANE Select
- NM_002444
- dbSNP
- rs745873198
- Type
- single nucleotide variant
- Location
- chrX:65729707 (GRCh38)
- Structure
- AlphaFold pLDDT 86.77 · 10 PDB
- Residue 154
- the ferm domain
Similar variants
- MSN p.Pro154Leu 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-pro154 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown