Is MSH2 p.Ser515fs (c.1543_1561del) pathogenic?

MSH2 p.Ser515fs (c.15431561del) is classified Pathogenic in MSH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-05-03). No gnomAD frequency available for this variant; Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with MSH2 p.Ser515fs (c.1543_1561del)?

MSH2 p.Ser515fs (c.1543_1561del) is associated with Hereditary nonpolyposis colorectal neoplasms (ClinVar).

How common is MSH2 p.Ser515fs (c.1543_1561del) in the general population?

MSH2 p.Ser515fs (c.1543_1561del) is no gnomAD frequency available for this variant (gnomAD).

MSH2 p.Ser515fs

c.1543_1561del · rs2104173353 · VCV1074953

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

Hereditary nonpolyposis colorectal neoplasms

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 0.41	GERP -3.4, 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.Ser515fs
Coding: c.1543_1561del
MANE Select: NM_000251
dbSNP: rs2104173353
Type: Deletion
Location: chr2:47466685 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 515: a β-strand

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

Disease context

Hereditary nonpolyposis colorectal neoplasms — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MSH2 p.Ser515= Benign/Likely benign ★★ same residue
MSH2 p.Ser515Cys Uncertain significance ★ ⚠ same residue
MSH2 p.Ser515Tyr Uncertain significance ★ ⚠ same residue
MSH2 c.1077-66_1146del Pathogenic/Likely pathogenic ★★ same condition
MSH2 c.1387-2del Pathogenic/Likely pathogenic ★★ same condition
MSH2 c.1906_2005+8del Pathogenic/Likely pathogenic ★★ same condition
MSH2 c.2005+3_2005+14del Likely pathogenic ★★ same condition
MSH2 c.207_211+42del 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-ser515fs (accessed [today's date]).

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