Is MSH2 p.Ala50= (c.150G>C) pathogenic?

MSH2 p.Ala50= (c.150G>C) is classified Benign/Likely benign in MSH2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-30). Very rare (popmax 6.22e-05%); Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with MSH2 p.Ala50= (c.150G>C)?

MSH2 p.Ala50= (c.150G>C) is associated with Hereditary nonpolyposis colorectal neoplasms, Lynch syndrome 1, hereditary neoplastic syndrome (ClinVar).

How common is MSH2 p.Ala50= (c.150G>C) in the general population?

MSH2 p.Ala50= (c.150G>C) is very rare (popmax 6.22e-05%) (gnomAD).

MSH2 p.Ala50=

c.150G>C · rs1672246989 · VCV1086969

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 6.22e-05%)

Conditions

Hereditary nonpolyposis colorectal neoplasms

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.37	GERP -1.6, phastCons 0.98
Overall
CADD	12.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.22e-05%

Overall 6.22e-05% 1/1,607,612 alleles · very rare exomes 1/1,455,234 · genomes 0/152,378 · 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: MSH2
Protein: p.Ala50=
Coding: c.150G>C
MANE Select: NM_000251
dbSNP: rs1672246989
Type: single nucleotide variant
Location: chr2:47403341 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 50: an α-helix

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 1 hereditary neoplastic syndrome

Similar variants

MSH2 p.Ala50Thr Uncertain significance ★★ ⚠ same residue
MSH2 p.Ala50Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Ala50Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Ala50Ser Uncertain significance ★ ⚠ same residue
MSH2 p.Ala50Val 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

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-ala50 (accessed [today's date]).

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