Is MSN p.Arg435Ter (c.1303C>T) pathogenic?

MSN p.Arg435Ter (c.1303C>T) is classified Pathogenic in MSN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). Absent from gnomAD v4.1.

How common is MSN p.Arg435Ter (c.1303C>T) in the general population?

MSN p.Arg435Ter (c.1303C>T) is absent from gnomAD v4.1 (gnomAD).

MSN p.Arg435Ter

c.1303C>T · rs2523021283 · VCV2101770

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.7, phastCons 1
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MSN
Protein: p.Arg435Ter
Coding: c.1303C>T
MANE Select: NM_002444
dbSNP: rs2523021283
Type: single nucleotide variant
Location: chrX:65738576 (GRCh38)
Structure: AlphaFold pLDDT 86.77 · 10 PDB

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

Similar variants

MSN p.Arg435Gln Uncertain significance ★ ⚠ same residue
MSN p.Arg435Pro 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-arg435ter (accessed [today's date]).

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