Is AXIN2 p.Ser461fs (c.1380_1381dup) pathogenic?

AXIN2 p.Ser461fs (c.13801381dup) is classified Pathogenic in AXIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-03). Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Ser461fs (c.1380_1381dup)?

AXIN2 p.Ser461fs (c.1380_1381dup) is associated with hereditary neoplastic syndrome (ClinVar).

AXIN2 p.Ser461fs

c.1380_1381dup · VCV3470415

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 6 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: AXIN2
Protein: p.Ser461fs
Coding: c.1380_1381dup
MANE Select: NM_004655
Type: Microsatellite
Location: chr17:65537654 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 461: the 'interaction with beta-catenin' region; the 'disordered' region

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.Ser461Arg Uncertain significance ★★ ⚠ same residue
AXIN2 p.Ser461Ile Uncertain significance ★★ ⚠ same residue
AXIN2 p.Ser461= Benign/Likely benign ★★ same residue
AXIN2 p.Ser461Gly Uncertain significance ★ ⚠ same residue
AXIN2 p.Leu255fs Pathogenic ★★ same condition
AXIN2 p.380KL[1] Uncertain significance ★★ same condition
AXIN2 p.463RS[3] Uncertain significance ★★ same condition
AXIN2 p.Arg388dup Uncertain significance ★★ 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-ser461fs (accessed [today's date]).

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