Is MSH3 p.Ser598= (c.1794G>A) pathogenic?

MSH3 p.Ser598= (c.1794G>A) is classified Benign/Likely benign in MSH3 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-03-01). Rare (popmax 0.255%, nfe); Associated with familial adenomatous polyposis 4.

What condition is associated with MSH3 p.Ser598= (c.1794G>A)?

MSH3 p.Ser598= (c.1794G>A) is associated with familial adenomatous polyposis 4, hereditary neoplastic syndrome (ClinVar).

How common is MSH3 p.Ser598= (c.1794G>A) in the general population?

MSH3 p.Ser598= (c.1794G>A) is rare (popmax 0.255%, nfe) (gnomAD).

How is MSH3-related polyposis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MSH3 p.Ser598=

c.1794G>A · rs61753791 · VCV718280

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.255%, nfe)

Conditions

familial adenomatous polyposis 4

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 -0.36	GERP -2.1, phastCons 0.3
Overall
CADD	11.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.255% European (non-Finnish) · 3,013/1,179,924 alleles

Filtering AF 0.248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.245%

Overall 0.199% 3,214/1,613,886 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.255%	392
Remaining individualsnot grpmax-eligible	0.214%	466
Admixed American	0.0483%	2,069
African / African-American	0.0347%	2,883
East Asian	0.00669%	14,958
Finnishnot grpmax-eligible	0.00625%	15,999
South Asian	0.00549%	18,212

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.Ser598=
Coding: c.1794G>A
MANE Select: NM_002439
dbSNP: rs61753791
Type: single nucleotide variant
Location: chr5:80761576 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.48 · 25 PDB
Residue 598: an α-helix

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

Disease context

familial adenomatous polyposis 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For MSH3-related polyposis (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

MSH3 p.Ser598Leu Uncertain significance ★★ ⚠ same residue
MSH3 p.Ser598Pro Uncertain significance ★★ ⚠ same residue
MSH3 p.Ser598Trp Uncertain significance ★★ ⚠ same residue
MSH3 p.Ser598fs Pathogenic ★ same residue
MSH3 c.1341-2A>C Likely pathogenic ★★ same condition
MSH3 c.1341-2A>G Likely pathogenic ★★ same condition
MSH3 c.1568+1G>A 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-ser598 (accessed [today's date]).

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