Is MSH2 p.Pro868fs (c.2601dup) pathogenic?

MSH2 p.Pro868fs (c.2601dup) is classified Pathogenic in MSH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-09). No gnomAD frequency available for this variant; Associated with Lynch syndrome 1.

What condition is associated with MSH2 p.Pro868fs (c.2601dup)?

MSH2 p.Pro868fs (c.2601dup) is associated with Lynch syndrome 1 (ClinVar).

How common is MSH2 p.Pro868fs (c.2601dup) in the general population?

MSH2 p.Pro868fs (c.2601dup) is no gnomAD frequency available for this variant (gnomAD).

How is Lynch syndrome inherited?

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

MSH2 p.Pro868fs

c.2601dup · rs2529039319 · VCV2673377

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

Lynch syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (15 of 16, 35 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.8	GERP 2.1, 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: MSH2
Protein: p.Pro868fs
Coding: c.2601dup
MANE Select: NM_000251
dbSNP: rs2529039319
Type: Duplication
Location: chr2:47480836 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 868: a UniProt-annotated variant site (in gastric cancer; uncertain significance); an α-helix

Full MSH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Lynch syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Lynch syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

MSH2 p.Pro868= Benign ★ same residue
MSH2 p.Gln402fs Pathogenic ★★★ same condition
MSH2 p.Glu12fs Pathogenic ★★★ same condition
MSH2 p.Gly195delinsGluGluThrArgThrValTer Pathogenic ★★★ same condition
MSH2 p.Met779fs Pathogenic ★★★ same condition
MSH2 p.Tyr563fs Pathogenic ★★★ same condition
MSH2 c.2005+8dup Likely benign ★★★ same condition
MSH2 c.1076+1dup 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/msh2-p-pro868fs (accessed [today's date]).

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