Is MSH3 p.Ser759= (c.2277T>C) pathogenic?

MSH3 p.Ser759= (c.2277T>C) is classified Likely benign in MSH3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-25). No allele count reported in gnomAD v4.1 (AN 1,585,038); Associated with hereditary neoplastic syndrome.

What condition is associated with MSH3 p.Ser759= (c.2277T>C)?

MSH3 p.Ser759= (c.2277T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MSH3 p.Ser759= (c.2277T>C) in the general population?

MSH3 p.Ser759= (c.2277T>C) is no allele count reported in gnomAD v4.1 (AN 1,585,038) (gnomAD).

MSH3 p.Ser759=

c.2277T>C · rs2112890147 · VCV1155367

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,585,038)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.084	GERP -2.3, phastCons 0.97
Overall
CADD	7.683	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,585,038). 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: MSH3
Protein: p.Ser759=
Coding: c.2277T>C
MANE Select: NM_002439
dbSNP: rs2112890147
Type: single nucleotide variant
Location: chr5:80775717 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 25 PDB
Residue 759: an α-helix

Full MSH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

MSH3 p.Ser759Ala Uncertain significance ★★ ⚠ same residue
MSH3 p.Ser759Cys Uncertain significance ★ ⚠ same residue
MSH3 p.Ser759fs Pathogenic/Likely pathogenic ★★ same residue
MSH3 p.Ser759Thr Uncertain significance ★ ⚠ same residue
MSH3 c.1341-2A>C Likely pathogenic ★★ same condition
MSH3 c.1341-2A>G Likely pathogenic ★★ same condition
MSH3 c.1568+1G>C Likely pathogenic ★★ same condition
MSH3 c.1653+1G>A 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/msh3-p-ser759 (accessed [today's date]).

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