Is MSN p.Ala148= (c.444C>T) pathogenic?

MSN p.Ala148= (c.444C>T) is classified Likely benign in MSN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). Ultra-rare (popmax 0.0628%, afr).

How common is MSN p.Ala148= (c.444C>T) in the general population?

MSN p.Ala148= (c.444C>T) is ultra-rare (popmax 0.0628%, afr) (gnomAD).

MSN p.Ala148=

c.444C>T · rs368950777 · VCV1603058

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0628%, 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 -3.5	GERP -3.4
Overall
CADD	3.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0628% African / African-American · 36/57,321 alleles

Filtering AF 0.0466% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.041%

Overall 0.00719% 87/1,209,353 alleles · ultra-rare exomes 82/1,097,114 · genomes 5/112,239 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0883%	1,133
African / African-Americangrpmax	0.0628%	1,592
South Asian	0.00353%	28,317
European (non-Finnish)	0.000782%	127,823

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala148=
Coding: c.444C>T
MANE Select: NM_002444
dbSNP: rs368950777
Type: single nucleotide variant
Location: chrX:65729689 (GRCh38)
Structure: AlphaFold pLDDT 86.77 · 10 PDB
Residue 148: the ferm domain; a turn

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

Similar variants

MSN p.Ala148Val Likely benign ★ 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-ala148 (accessed [today's date]).

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