Is AXIN2 p.Cys241fs (c.722_743del) pathogenic?

AXIN2 p.Cys241fs (c.722743del) is classified Pathogenic in AXIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Cys241fs (c.722_743del)?

AXIN2 p.Cys241fs (c.722_743del) is associated with hereditary neoplastic syndrome (ClinVar).

AXIN2 p.Cys241fs

c.722_743del · VCV3981040

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.65	GERP -2.8, phastCons 0.94

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: AXIN2
Protein: p.Cys241fs
Coding: c.722_743del
MANE Select: NM_004655
Type: Deletion
Location: chr17:65557878 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB

Full AXIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

AXIN2 p.Cys241Tyr Uncertain significance ★★ ⚠ same residue
AXIN2 p.Cys241= Benign/Likely benign ★★ same residue
AXIN2 p.Cys241Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
AXIN2 p.Ala417fs Pathogenic ★★ same condition
AXIN2 p.Ala492fs Pathogenic/Likely pathogenic ★★ same condition
AXIN2 p.Asn344fs Pathogenic ★★ same condition
AXIN2 p.Gly546fs Pathogenic ★★ same condition
AXIN2 p.Lys554fs 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/axin2-p-cys241fs (accessed [today's date]).

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