Is MSH6 p.Pro293fs (c.878_883delinsTTCG) pathogenic?

MSH6 p.Pro293fs (c.878883delinsTTCG) is classified Pathogenic/Likely pathogenic in MSH6 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-09-16). No gnomAD frequency available for this variant; Associated with Lynch syndrome 5.

What condition is associated with MSH6 p.Pro293fs (c.878_883delinsTTCG)?

MSH6 p.Pro293fs (c.878_883delinsTTCG) is associated with Lynch syndrome 5, endometrial carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is MSH6 p.Pro293fs (c.878_883delinsTTCG) in the general population?

MSH6 p.Pro293fs (c.878_883delinsTTCG) 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.

MSH6 p.Pro293fs

c.878_883delinsTTCG · rs1114167748 · VCV428369

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Lynch syndrome 5

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 4 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 0.007, phastCons 0.95

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: MSH6
Protein: p.Pro293fs
Coding: c.878_883delinsTTCG
MANE Select: NM_000179
dbSNP: rs1114167748
Type: Indel
Location: chr2:47798861 (GRCh38)
Gene constraint: LOEUF 0.841 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 77.93 · 8 PDB
Residue 293: the 'disordered' region

Full MSH6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Lynch syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: endometrial carcinoma hereditary neoplastic syndrome

For Lynch syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

MSH6 p.Pro293Leufs Pathogenic ★ same residue
MSH6 p.Pro293Arg Uncertain significance ★★ ⚠ same residue
MSH6 p.Pro293Leu Uncertain significance ★★ ⚠ same residue
MSH6 p.Pro293Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH6 p.Pro293Thr Uncertain significance ★ ⚠ same residue
MSH6 c.3802-15_3802delinsAAGCTAATAGCA Likely pathogenic ★★ same condition
MSH6 p.Asp390fs Pathogenic ★★ same condition
MSH6 p.Asp392fs 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/msh6-p-pro293fs (accessed [today's date]).

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