Is MSH2 p.Val155Asp (c.464T>A) pathogenic?

MSH2 p.Val155Asp (c.464T>A) is classified Uncertain significance in MSH2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-11-18). AlphaMissense: likely benign (0.2485); Absent from gnomAD v4.1; Associated with Hereditary nonpolyposis colorectal neoplasms.

What condition is associated with MSH2 p.Val155Asp (c.464T>A)?

MSH2 p.Val155Asp (c.464T>A) is associated with Hereditary nonpolyposis colorectal neoplasms, Lynch syndrome, Lynch syndrome 1 (ClinVar).

How common is MSH2 p.Val155Asp (c.464T>A) in the general population?

MSH2 p.Val155Asp (c.464T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MSH2 p.Val155Asp (c.464T>A)?

AlphaMissense predicts likely benign (score 0.2485) — an in-silico prediction, not a clinical call.

MSH2 p.Val155Asp

c.464T>A · rs876658188 · VCV229776

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2485 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Hereditary nonpolyposis colorectal neoplasms

Computational evidence

Protein change
AlphaMissense	0.2485	likely benign
REVEL	0.514	indeterminate
SaProt	LLR -10.34	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.2	GERP 1.4, phastCons 1
Regional constraint	o/e 1.30	unconstrained · MANE · 80 kb · p 4.9e-24 · regional, not allelic
Overall
CADD	14.67	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MSH2
Protein: p.Val155Asp
Coding: c.464T>A
MANE Select: NM_000251
dbSNP: rs876658188
Type: single nucleotide variant
Location: chr2:47410191 (GRCh38)
Gene constraint: LOEUF 0.672 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.60 · 30 PDB
Residue 155: 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.Val155Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Val155Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Val155Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
MSH2 p.Val155Phe Uncertain significance ★ ⚠ same residue
MSH2 p.Val155fs 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-val155asp (accessed [today's date]).

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