Is MSH2 p.Lys113= (c.339G>A) pathogenic?

MSH2 p.Lys113= (c.339G>A) is classified Benign in MSH2 (ClinVar, Expert panel, 33 submitters; last evaluated 2013-09-05). Rare (popmax 0.617%, nfe); Associated with Lynch syndrome.

What condition is associated with MSH2 p.Lys113= (c.339G>A)?

MSH2 p.Lys113= (c.339G>A) is associated with Lynch syndrome, Lynch syndrome 1, hereditary neoplastic syndrome (ClinVar).

How common is MSH2 p.Lys113= (c.339G>A) in the general population?

MSH2 p.Lys113= (c.339G>A) is rare (popmax 0.617%, nfe) (gnomAD).

How is Lynch syndrome inherited?

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

MSH2 p.Lys113=

c.339G>A · rs35898375 · VCV36576

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 33 submitters

gnomAD v4.1

Rare

rare (popmax 0.617%, nfe)

Conditions

Lynch syndrome

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 2.8	GERP 0.67, phastCons 1
Overall
CADD	7.765	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.617% European (non-Finnish) · 7,259/1,175,944 alleles

Filtering AF 0.605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.601%

Overall 0.5% 8,040/1,609,290 alleles · rare exomes 7,572/1,457,184 · genomes 468/152,106 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.617%	162
Remaining individualsnot grpmax-eligible	0.535%	187
Finnishnot grpmax-eligible	0.181%	552
Admixed American	0.172%	582
Ashkenazi Jewishnot grpmax-eligible	0.156%	643
Middle Eastern	0.133%	750
African / African-American	0.12%	832
South Asian	0.0935%	1,070

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.Lys113=
Coding: c.339G>A
MANE Select: NM_000251
dbSNP: rs35898375
Type: single nucleotide variant
Location: chr2:47408528 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB

Full MSH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Lynch syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Lynch syndrome 1 hereditary neoplastic syndrome

For Lynch syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

MSH2 p.Lys113Glu Uncertain significance ★★ ⚠ same residue
MSH2 p.Lys113Ter Pathogenic ★ same residue
MSH2 p.Lys113Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Lys113Asn Uncertain significance ★★ ⚠ same residue
MSH2 p.Lys113Gln 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

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-lys113 (accessed [today's date]).

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