Is MSH3 p.Pro72fs (c.215del) pathogenic?

MSH3 p.Pro72fs (c.215del) is classified Pathogenic/Likely pathogenic in MSH3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-09). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MSH3 p.Pro72fs (c.215del)?

MSH3 p.Pro72fs (c.215del) is associated with hereditary neoplastic syndrome, endometrial carcinoma (ClinVar).

How common is MSH3 p.Pro72fs (c.215del) in the general population?

MSH3 p.Pro72fs (c.215del) is absent from gnomAD v4.1 (gnomAD).

MSH3 p.Pro72fs

c.215del · rs1749220884 · VCV1786872

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,466,618)

Conditions

hereditary neoplastic syndrome

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 1 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.85	GERP -2.3

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,466,618). 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.Pro72fs
Coding: c.215del
MANE Select: NM_002439
dbSNP: rs1749220884
Type: Deletion
Location: chr5:80654940 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 25 PDB
Residue 72: the 'disordered' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: endometrial carcinoma

Similar variants

MSH3 p.Pro72Leu Uncertain significance ★★ ⚠ same residue
MSH3 p.Pro72Ser Uncertain significance ★★ ⚠ same residue
MSH3 p.Pro72= Likely benign ★ same residue
MSH3 c.2253+3_2253+7del Pathogenic/Likely pathogenic ★★ same condition
MSH3 c.2814delG Pathogenic ★★ same condition
MSH3 c.2988_3000+893del Likely pathogenic ★★ same condition
MSH3 p.Ala283fs Pathogenic ★★ same condition
MSH3 p.Ala44fs Pathogenic/Likely 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-pro72fs (accessed [today's date]).

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