Is AXIN2 p.Arg463Pro (c.1386_1388delinsTCC) pathogenic?

AXIN2 p.Arg463Pro (c.13861388delinsTCC) is classified Uncertain significance in AXIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Arg463Pro (c.1386_1388delinsTCC)?

AXIN2 p.Arg463Pro (c.1386_1388delinsTCC) is associated with hereditary neoplastic syndrome (ClinVar).

AXIN2 p.Arg463Pro

c.1386_1388delinsTCC · VCV3335403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 25 kb · p 0.011 · regional, not allelic

Variant & gene context

Gene: AXIN2
Protein: p.Arg463Pro
Coding: c.1386_1388delinsTCC
MANE Select: NM_004655
Type: Indel
Location: chr17:65537648 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 463: 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.Arg463_Ser464insProArg Uncertain significance ★ same residue
AXIN2 p.Arg463His Uncertain significance ★ same residue
AXIN2 p.Arg463Cys Uncertain significance ★★ ⚠ same residue
AXIN2 p.Arg463Leu Uncertain significance ★★ ⚠ same residue
AXIN2 p.Arg463= Likely benign ★★ same residue
AXIN2 p.Arg463Gly Uncertain significance ★ same residue
AXIN2 p.Arg463Ser Uncertain significance ★ same residue
AXIN2 p.Gly665fs 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-arg463pro (accessed [today's date]).

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