Is MSN p.Ser144Pro (c.430T>C) pathogenic?

MSN p.Ser144Pro (c.430T>C) is classified Uncertain significance in MSN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-12). AlphaMissense: likely benign (0.0502); Very rare (popmax 0.00524%, afr).

How common is MSN p.Ser144Pro (c.430T>C) in the general population?

MSN p.Ser144Pro (c.430T>C) is very rare (popmax 0.00524%, afr) (gnomAD).

What do computational predictors say about MSN p.Ser144Pro (c.430T>C)?

AlphaMissense predicts likely benign (score 0.0502) — an in-silico prediction, not a clinical call.

MSN p.Ser144Pro

c.430T>C · VCV3624505

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0502 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00524%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0502	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -4.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.95	GERP 0.48, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 64 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	13.83	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00524% African / African-American · 3/57,291 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000685%

Overall 0.000579% 7/1,209,753 alleles · very rare exomes 5/1,097,547 · genomes 2/112,206 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00524%	19,097
European (non-Finnish)	0.000447%	223,755

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.Ser144Pro
Coding: c.430T>C
MANE Select: NM_002444
Type: single nucleotide variant
Location: chrX:65729675 (GRCh38)
Structure: AlphaFold pLDDT 86.77 · 10 PDB
Residue 144: the ferm domain; a turn

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

Similar variants

MSN p.Ser144Cys Uncertain significance ★★ ⚠ same residue
MSN p.Ser144Thr 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

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-ser144pro (accessed [today's date]).

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