Is MSH2 p.Phe519fs (c.1557_1567delinsACACAG) pathogenic?

MSH2 p.Phe519fs (c.15571567delinsACACAG) is classified Pathogenic in MSH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). No gnomAD frequency available for this variant; Associated with Lynch syndrome 1.

What condition is associated with MSH2 p.Phe519fs (c.1557_1567delinsACACAG)?

MSH2 p.Phe519fs (c.1557_1567delinsACACAG) is associated with Lynch syndrome 1 (ClinVar).

How common is MSH2 p.Phe519fs (c.1557_1567delinsACACAG) in the general population?

MSH2 p.Phe519fs (c.1557_1567delinsACACAG) 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.Phe519fs

c.1557_1567delinsACACAG · rs2528750839 · VCV2673355

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	predicted	premature termination codon in exon 10 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.71	GERP -2, 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.Phe519fs
Coding: c.1557_1567delinsACACAG
MANE Select: NM_000251
dbSNP: rs2528750839
Type: Indel
Location: chr2:47466704 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 519: a turn; a UniProt-annotated variant site (in lynch1; uncertain significance; normal mismatch repair activity)

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.Phe519= Conflicting classifications of pathogenicity ★ same residue
MSH2 p.Met492_Gln493delinsIleTer Pathogenic ★★★ same condition
MSH2 p.Pro349Arg Likely pathogenic ★★★ same condition
MSH2 p.Asp156fs Pathogenic ★★ same condition
MSH2 p.Gln4fs Pathogenic ★★ same condition
MSH2 p.Glu529fs Pathogenic ★★ same condition
MSH2 p.Gly164fs Pathogenic ★★ same condition
MSH2 p.Gly410fs 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-phe519fs (accessed [today's date]).

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