Is MSN p.Pro265= (c.795G>A) pathogenic?

MSN p.Pro265= (c.795G>A) is classified Uncertain significance in MSN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-09). Very rare (popmax 0.000113%, nfe).

How common is MSN p.Pro265= (c.795G>A) in the general population?

MSN p.Pro265= (c.795G>A) is very rare (popmax 0.000113%, nfe) (gnomAD).

MSN p.Pro265=

c.795G>A · VCV4951160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000113%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.82	donor gain · deltas
Pangolin	Δ0.60	loss · gain 0.40 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 3.6	GERP -1.6, phastCons 1
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000113% European (non-Finnish) · 1/882,018 alleles

Overall 8.35e-05% 1/1,196,935 alleles · very rare exomes 1/1,083,109 · genomes 0/113,826 · joint denominator

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.Pro265=
Coding: c.795G>A
MANE Select: NM_002444
Type: single nucleotide variant
Location: chrX:65733280 (GRCh38)
Structure: AlphaFold pLDDT 86.77 · 10 PDB
Residue 265: the ferm domain

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

Similar variants

MSN p.Pro265Leu 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-pro265 (accessed [today's date]).

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