Is MSH2 p.Val705fs (c.2113del) pathogenic?

MSH2 p.Val705fs (c.2113del) is classified Pathogenic in MSH2 (ClinVar, Expert panel, 12 submitters; last evaluated 2013-09-05). No gnomAD frequency available for this variant; Associated with Lynch syndrome.

What condition is associated with MSH2 p.Val705fs (c.2113del)?

MSH2 p.Val705fs (c.2113del) is associated with Lynch syndrome, Lynch syndrome 1, hereditary neoplastic syndrome (ClinVar).

How common is MSH2 p.Val705fs (c.2113del) in the general population?

MSH2 p.Val705fs (c.2113del) 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.Val705fs

c.2113del · rs63749811 · VCV1760

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 12 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 13 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.2	GERP -1.8, phastCons 0.002

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.Val705fs
Coding: c.2113del
MANE Select: NM_000251
dbSNP: rs63749811
Type: Deletion
Location: chr2:47476474 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB

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

Also linked: Lynch syndrome 1 hereditary neoplastic syndrome hereditary nonpolyposis colon cancer

For Lynch syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

MSH2 p.Val705= Benign/Likely benign ★★ same residue
MSH2 p.Val705Met Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 c.1077-?_1386+?del Pathogenic ★★★ same condition
MSH2 c.1077-?_1661+?del Pathogenic ★★★ same condition
MSH2 c.1077-?_2005+?del Pathogenic ★★★ same condition
MSH2 c.1077-220_1276+6245del Pathogenic ★★★ same condition
MSH2 c.1077-?_(*272_? Pathogenic ★★★ same condition
MSH2 c.(1276+1_1277-1 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-val705fs (accessed [today's date]).

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