Is AXIN2 p.Arg463= (c.1389C>A) pathogenic?

AXIN2 p.Arg463= (c.1389C>A) is classified Likely benign in AXIN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-29). Very rare (popmax 0.00134%, afr); Associated with oligodontia-cancer predisposition syndrome.

What condition is associated with AXIN2 p.Arg463= (c.1389C>A)?

AXIN2 p.Arg463= (c.1389C>A) is associated with oligodontia-cancer predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is AXIN2 p.Arg463= (c.1389C>A) in the general population?

AXIN2 p.Arg463= (c.1389C>A) is very rare (popmax 0.00134%, afr) (gnomAD).

AXIN2 p.Arg463=

c.1389C>A · rs878854721 · VCV1157718

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

oligodontia-cancer predisposition syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.7	GERP -3.7
Overall
CADD	5.279	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,508 alleles

Overall 0.000658% 1/152,006 alleles · very rare

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: AXIN2
Protein: p.Arg463=
Coding: c.1389C>A
MANE Select: NM_004655
dbSNP: rs878854721
Type: single nucleotide variant
Location: chr17:65537647 (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

oligodontia-cancer predisposition syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

Similar variants

AXIN2 p.Arg463Cys Uncertain significance ★★ ⚠ same residue
AXIN2 p.Arg463Leu Uncertain significance ★★ ⚠ same residue
AXIN2 p.Arg463fs Pathogenic ★ same residue
AXIN2 p.Arg463_Ser464insProArg Uncertain significance ★ same residue
AXIN2 p.Arg463Gly Uncertain significance ★ same residue
AXIN2 p.Arg463His Uncertain significance ★ same residue
AXIN2 p.Arg463Pro Uncertain significance ★ same residue
AXIN2 p.Arg463Ser Uncertain significance ★ same residue

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-arg463 (accessed [today's date]).

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