Is AXIN2 p.Pro494fs (c.1460_1472dup) pathogenic?

AXIN2 p.Pro494fs (c.14601472dup) is classified Pathogenic in AXIN2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-05-17). Absent from gnomAD; Associated with Oligodontia.

What condition is associated with AXIN2 p.Pro494fs (c.1460_1472dup)?

AXIN2 p.Pro494fs (c.1460_1472dup) is associated with Oligodontia, colorectal cancer, oligodontia-cancer predisposition syndrome (ClinVar).

How common is AXIN2 p.Pro494fs (c.1460_1472dup) in the general population?

AXIN2 p.Pro494fs (c.1460_1472dup) is absent from gnomAD (gnomAD).

AXIN2 p.Pro494fs

c.1460_1472dup · rs1567755946 · VCV599333

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Oligodontia

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 -3.4	GERP -3.1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AXIN2
Protein: p.Pro494fs
Coding: c.1460_1472dup
MANE Select: NM_004655
dbSNP: rs1567755946
Type: Duplication
Location: chr17:65537563 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 494: the 'disordered' region

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

Disease context

Oligodontia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colorectal cancer oligodontia-cancer predisposition syndrome

Similar variants

AXIN2 p.Pro494Arg Uncertain significance ★★ ⚠ same residue
AXIN2 p.Pro494= Benign/Likely benign ★★ same residue
AXIN2 p.Pro494Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
AXIN2 p.Pro494Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
AXIN2 p.Arg256fs Pathogenic ★★ same condition
AXIN2 p.Arg675fs Pathogenic ★★ same condition
AXIN2 p.Asp268Ter Pathogenic ★★ same condition
AXIN2 p.His83fs 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-pro494fs (accessed [today's date]).

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