Is MSH3 p.Pro66= (c.198C>G) pathogenic?

MSH3 p.Pro66= (c.198C>G) is classified Likely benign in MSH3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-19). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MSH3 p.Pro66= (c.198C>G)?

MSH3 p.Pro66= (c.198C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MSH3 p.Pro66= (c.198C>G) in the general population?

MSH3 p.Pro66= (c.198C>G) is absent from gnomAD v4.1 (gnomAD).

MSH3 p.Pro66=

c.198C>G · rs1435558278 · VCV1106530

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.35	GERP 1.6, phastCons 0.61
Overall
CADD	9.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MSH3
Protein: p.Pro66=
Coding: c.198C>G
MANE Select: NM_002439
dbSNP: rs1435558278
Type: single nucleotide variant
Location: chr5:80654925 (GRCh38)

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

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-pro66 (accessed [today's date]).

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