Is MSH3 p.Ser804= (c.2412T>C) pathogenic?

MSH3 p.Ser804= (c.2412T>C) is classified Likely benign in MSH3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-05). Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with MSH3 p.Ser804= (c.2412T>C)?

MSH3 p.Ser804= (c.2412T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MSH3 p.Ser804= (c.2412T>C) in the general population?

MSH3 p.Ser804= (c.2412T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

MSH3 p.Ser804=

c.2412T>C · rs1377891964 · VCV2498973

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -1.5	GERP -0.54
Overall
CADD	5.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,756 alleles

Overall 6.28e-05% 1/1,592,988 alleles · very rare exomes 1/1,440,680 · genomes 0/152,308 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MSH3
Protein: p.Ser804=
Coding: c.2412T>C
MANE Select: NM_002439
dbSNP: rs1377891964
Type: single nucleotide variant
Location: chr5:80778813 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 25 PDB
Residue 804: 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.Ser804Gly Uncertain significance ★★ ⚠ same residue
MSH3 p.Ser804Thr Uncertain significance ★★ ⚠ same residue
MSH3 p.Ser804Arg Uncertain significance ★ ⚠ same residue
MSH3 p.Ser804Asn Likely benign ★ same residue
MSH3 p.Ser804Ile 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

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-ser804 (accessed [today's date]).

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