Is MSH3 p.Lys714fs (c.2141del) pathogenic?

MSH3 p.Lys714fs (c.2141del) is classified Pathogenic in MSH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-30). Absent from gnomAD; Associated with familial adenomatous polyposis 4.

What condition is associated with MSH3 p.Lys714fs (c.2141del)?

MSH3 p.Lys714fs (c.2141del) is associated with familial adenomatous polyposis 4 (ClinVar).

How common is MSH3 p.Lys714fs (c.2141del) in the general population?

MSH3 p.Lys714fs (c.2141del) is absent from gnomAD (gnomAD).

How is MSH3-related polyposis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MSH3 p.Lys714fs

c.2141del · rs751236312 · VCV2673509

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

familial adenomatous polyposis 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MSH3
Protein: p.Lys714fs
Coding: c.2141del
MANE Select: NM_002439
dbSNP: rs751236312
Type: Deletion
Location: chr5:80768886 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 25 PDB
Residue 714: an α-helix

Full MSH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial adenomatous polyposis 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MSH3-related polyposis (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

MSH3 p.Lys714del Uncertain significance ★ same residue
MSH3 c.1564_1568+18del Pathogenic/Likely pathogenic ★★ same condition
MSH3 c.2814delG Pathogenic ★★ same condition
MSH3 p.Ala283fs Pathogenic ★★ same condition
MSH3 p.Arg85fs Pathogenic ★★ same condition
MSH3 p.Asn591fs Pathogenic ★★ same condition
MSH3 p.Asn880fs Pathogenic ★★ same condition
MSH3 p.Asp1051fs Pathogenic ★★ same condition

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/msh3-p-lys714fs (accessed [today's date]).

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