Is MSH2 p.Ala207Ser (c.619G>T) pathogenic?

MSH2 p.Ala207Ser (c.619G>T) is classified Uncertain significance in MSH2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-09-17). AlphaMissense: likely benign (0.0756); Very rare (popmax 6.2e-05%); Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with MSH2 p.Ala207Ser (c.619G>T)?

MSH2 p.Ala207Ser (c.619G>T) is associated with Hereditary nonpolyposis colorectal neoplasms, Lynch syndrome, hereditary neoplastic syndrome (ClinVar).

How common is MSH2 p.Ala207Ser (c.619G>T) in the general population?

MSH2 p.Ala207Ser (c.619G>T) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about MSH2 p.Ala207Ser (c.619G>T)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

MSH2 p.Ala207Ser

c.619G>T · rs63750913 · VCV479819

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Hereditary nonpolyposis colorectal neoplasms

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.447	indeterminate
SaProt	LLR -4.81	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.7	GERP -1.3, phastCons 0.96
Regional constraint	o/e 1.30	unconstrained · MANE · 80 kb · p 4.9e-24 · regional, not allelic
Overall
CADD	7.365	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,062 alleles · very rare exomes 1/1,461,746 · genomes 0/152,316 · 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.Ala207Ser
Coding: c.619G>T
MANE Select: NM_000251
dbSNP: rs63750913
Type: single nucleotide variant
Location: chr2:47410346 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 207: 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 hereditary neoplastic syndrome

Similar variants

MSH2 p.Ala207Val Likely benign ★★ same residue
MSH2 p.Ala207Pro Uncertain significance ★ ⚠ same residue
MSH2 p.Ala207Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Ala207delinsGlyTer Pathogenic ★ same residue
MSH2 p.Ala207fs Pathogenic ★ 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-ala207ser (accessed [today's date]).

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