Is MSH3 p.Pro147fs (c.438_439delinsG) pathogenic?

MSH3 p.Pro147fs (c.438439delinsG) is classified Pathogenic in MSH3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-01). Absent from gnomAD; Associated with familial adenomatous polyposis 4.

What condition is associated with MSH3 p.Pro147fs (c.438_439delinsG)?

MSH3 p.Pro147fs (c.438_439delinsG) is associated with familial adenomatous polyposis 4 (ClinVar).

How common is MSH3 p.Pro147fs (c.438_439delinsG) in the general population?

MSH3 p.Pro147fs (c.438_439delinsG) 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.Pro147fs

c.438_439delinsG · rs2546717431 · VCV2673510

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 3 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.3	GERP -3.6, phastCons 0.049

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.Pro147fs
Coding: c.438_439delinsG
MANE Select: NM_002439
dbSNP: rs2546717431
Type: Indel
Location: chr5:80665222 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 25 PDB
Residue 147: the 'interaction with exo1' region

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.Pro147Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH3 c.2654_2655+13delinsTATTTGG Likely pathogenic ★★ same condition
MSH3 p.Ile931fs Pathogenic ★★ same condition
MSH3 p.Leu439fs Pathogenic ★★ same condition
MSH3 p.Pro147Ala Uncertain significance ★★ ⚠ same residue
MSH3 c.1653+2_1653+3delinsGT Likely pathogenic ★ same condition
MSH3 p.Ala1045fs Pathogenic ★ same condition
MSH3 p.Arg623fs 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-pro147fs (accessed [today's date]).

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