Is AXIN2 p.Ala133= (c.399G>T) pathogenic?

AXIN2 p.Ala133= (c.399G>T) is classified Benign in AXIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). Absent from gnomAD v4.1; Associated with oligodontia-cancer predisposition syndrome.

What condition is associated with AXIN2 p.Ala133= (c.399G>T)?

AXIN2 p.Ala133= (c.399G>T) is associated with oligodontia-cancer predisposition syndrome (ClinVar).

How common is AXIN2 p.Ala133= (c.399G>T) in the general population?

AXIN2 p.Ala133= (c.399G>T) is absent from gnomAD v4.1 (gnomAD).

AXIN2 p.Ala133=

c.399G>T · rs754867315 · VCV3254320

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -7.5	GERP -3.9
Overall
CADD	2.656	PHRED · no single calibrated threshold — expert panels disagree

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: AXIN2
Protein: p.Ala133=
Coding: c.399G>T
MANE Select: NM_004655
dbSNP: rs754867315
Type: single nucleotide variant
Location: chr17:65558222 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 133: the rgs domain

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

Similar variants

AXIN2 p.Ala133Pro Uncertain significance ★★ ⚠ same residue
AXIN2 p.Ala133Val Uncertain significance ★★ ⚠ same residue
AXIN2 p.Ala133Ser Uncertain significance ★ ⚠ same residue
AXIN2 c.1060-1G>C Likely pathogenic ★★ same condition
AXIN2 c.1200+1G>A Likely pathogenic ★★ same condition
AXIN2 c.1201-1G>C Likely pathogenic ★★ same condition
AXIN2 c.1713-1G>A Likely pathogenic ★★ same condition
AXIN2 c.815+1G>A Pathogenic/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/axin2-p-ala133 (accessed [today's date]).

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