Is MSH3 p.Ala52fs (c.147_154dup) pathogenic?

MSH3 p.Ala52fs (c.147154dup) is classified Pathogenic in MSH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with MSH3 p.Ala52fs (c.147_154dup)?

MSH3 p.Ala52fs (c.147_154dup) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MSH3 p.Ala52fs (c.147_154dup) in the general population?

MSH3 p.Ala52fs (c.147_154dup) is no gnomAD frequency available for this variant (gnomAD).

MSH3 p.Ala52fs

c.147_154dup · rs2546710148 · VCV2451077

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

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.66	GERP -3.6

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.Ala52fs
Coding: c.147_154dup
MANE Select: NM_000791 · reported on NM_002439
dbSNP: rs2546710148
Type: Duplication
Location: chr5:80654873 (GRCh38)

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

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-ala52fs (accessed [today's date]).

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