Is MSH3 p.Phe291fs (c.870dup) pathogenic?

MSH3 p.Phe291fs (c.870dup) is classified Pathogenic in MSH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-29). Absent from gnomAD; Associated with familial adenomatous polyposis 4.

What condition is associated with MSH3 p.Phe291fs (c.870dup)?

MSH3 p.Phe291fs (c.870dup) is associated with familial adenomatous polyposis 4 (ClinVar).

How common is MSH3 p.Phe291fs (c.870dup) in the general population?

MSH3 p.Phe291fs (c.870dup) 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.Phe291fs

c.870dup · rs2546722440 · VCV2673569

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 5 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, 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.Phe291fs
Coding: c.870dup
MANE Select: NM_002439
dbSNP: rs2546722440
Type: Duplication
Location: chr5:80672320 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 25 PDB
Residue 291: the 'interaction with exo1' region; 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.Arg715fs Pathogenic/Likely pathogenic ★★ same condition
MSH3 p.Asn385fs Pathogenic/Likely pathogenic ★★ same condition
MSH3 p.Asn550fs Pathogenic/Likely pathogenic ★★ same condition
MSH3 p.Asn613fs Pathogenic ★★ same condition
MSH3 p.Asn739fs Pathogenic ★★ same condition
MSH3 p.Asp698fs Pathogenic ★★ same condition
MSH3 p.Cys633fs Pathogenic ★★ same condition
MSH3 p.Gln192fs 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-phe291fs (accessed [today's date]).

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