Is MSH2 p.Val702= (c.2106G>A) pathogenic?

MSH2 p.Val702= (c.2106G>A) is classified Conflicting classifications of pathogenicity in MSH2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-04-14). Ultra-rare (popmax 0.0164%, mid); Associated with Hereditary nonpolyposis colorectal neoplasms.

How common is MSH2 p.Val702= (c.2106G>A) in the general population?

MSH2 p.Val702= (c.2106G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

MSH2 p.Val702=

Q: What condition is associated with MSH2 p.Val702= (c.2106G>A)?

MSH2 p.Val702= (c.2106G>A) is associated with Hereditary nonpolyposis colorectal neoplasms, Lynch syndrome, Lynch syndrome 1 (ClinVar).

c.2106G>A · rs786201108 · VCV183845

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 1.6	GERP -2.1, phastCons 1
Overall
CADD	6.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000496% 8/1,614,084 alleles · ultra-rare exomes 7/1,461,882 · genomes 1/152,202 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00133%	74,930
European (non-Finnish)	0.000424%	236,008

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.Val702=
Coding: c.2106G>A
MANE Select: NM_000251
dbSNP: rs786201108
Type: single nucleotide variant
Location: chr2:47476467 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 702: 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 hereditary neoplastic syndrome

Similar variants

MSH2 p.Val702Gly Uncertain significance ★★ ⚠ same residue
MSH2 p.Val702Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Val702Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Val702Met Conflicting classifications of pathogenicity ★ ⚠ 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

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-val702 (accessed [today's date]).

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