Is MSH2 p.Ala207fs (c.616_617dup) pathogenic?

MSH2 p.Ala207fs (c.616617dup) is classified Pathogenic in MSH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2012-05-10). Associated with Lynch syndrome.

What condition is associated with MSH2 p.Ala207fs (c.616_617dup)?

MSH2 p.Ala207fs (c.616_617dup) is associated with Lynch syndrome (ClinVar).

How is Lynch syndrome inherited?

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

MSH2 p.Ala207fs

c.616_617dup · VCV3779912

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Lynch syndrome

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	predicted	premature termination codon in exon 3 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP 1.7, phastCons 1

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

Variant & gene context

Gene: MSH2
Protein: p.Ala207fs
Coding: c.616_617dup
MANE Select: NM_000251
Type: Duplication
Location: chr2:47410342 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 207: a β-strand

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

Disease context

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

For Lynch syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

MSH2 p.Ala207Ser Uncertain significance ★★ ⚠ same residue
MSH2 c.1077-?_1276+?dup200 Pathogenic ★★★ same condition
MSH2 c.1077-135_1276+119dup Pathogenic ★★★ same condition
MSH2 c.1387-?_1661+?dup275 Pathogenic ★★★ same condition
MSH2 p.Ala398fs Pathogenic ★★★ same condition
MSH2 p.Ala834fs Pathogenic ★★★ same condition
MSH2 p.Gln402fs Pathogenic ★★★ same condition
MSH2 p.Glu12fs 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-ala207fs (accessed [today's date]).

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