Is MSH2 p.Pro202= (c.606C>G) pathogenic?

MSH2 p.Pro202= (c.606C>G) is classified Conflicting classifications of pathogenicity in MSH2 (ClinVar, Conflicting submitters, 13 submitters; last evaluated 2025-12-31). Ultra-rare (popmax 0.0414%, afr); Associated with Hereditary nonpolyposis colorectal neoplasms.

How common is MSH2 p.Pro202= (c.606C>G) in the general population?

MSH2 p.Pro202= (c.606C>G) is ultra-rare (popmax 0.0414%, afr) (gnomAD).

MSH2 p.Pro202=

Q: What condition is associated with MSH2 p.Pro202= (c.606C>G)?

MSH2 p.Pro202= (c.606C>G) is associated with Hereditary nonpolyposis colorectal neoplasms, Lynch syndrome, Lynch syndrome 1 (ClinVar).

c.606C>G · rs63750600 · VCV183729

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0414%, afr)

Conditions

Hereditary nonpolyposis colorectal neoplasms

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 -2.3	GERP -3.5
Overall
CADD	0.899	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0414% African / African-American · 31/74,856 alleles

Filtering AF 0.0299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00229% 37/1,613,864 alleles · ultra-rare exomes 13/1,461,808 · genomes 24/152,056 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0414%	2,415
Remaining individualsnot grpmax-eligible	0.0048%	20,827
East Asian	0.00445%	22,449
Admixed American	0.00167%	59,974

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: MSH2
Protein: p.Pro202=
Coding: c.606C>G
MANE Select: NM_000251
dbSNP: rs63750600
Type: single nucleotide variant
Location: chr2:47410333 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 202: 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

Also linked: Lynch syndrome Lynch syndrome 1 Muir-Torre syndrome hereditary neoplastic syndrome mismatch repair cancer syndrome 2

Similar variants

MSH2 p.Pro202Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Pro202Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Pro202Ser Uncertain significance ★ ⚠ same residue
MSH2 c.1076+1G>A Pathogenic ★★★ same condition
MSH2 c.1076+1G>T Likely pathogenic ★★★ same condition
MSH2 c.1077-1G>C Likely pathogenic ★★★ same condition
MSH2 c.1077-1G>T Likely pathogenic ★★★ same condition
MSH2 c.1077-2A>C 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-pro202 (accessed [today's date]).

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