Is AXIN2 p.Ala417fs (c.1249del) pathogenic?

AXIN2 p.Ala417fs (c.1249del) is classified Pathogenic in AXIN2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-13). Absent from gnomAD v4.1; Associated with oligodontia-cancer predisposition syndrome.

What condition is associated with AXIN2 p.Ala417fs (c.1249del)?

AXIN2 p.Ala417fs (c.1249del) is associated with oligodontia-cancer predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is AXIN2 p.Ala417fs (c.1249del) in the general population?

AXIN2 p.Ala417fs (c.1249del) is absent from gnomAD v4.1 (gnomAD).

AXIN2 p.Ala417fs

c.1249del · rs2043961707 · VCV936374

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,586,620)

Conditions

oligodontia-cancer predisposition 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 0.072	GERP -1.5

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,586,620). 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.Ala417fs
Coding: c.1249del
MANE Select: NM_004655
dbSNP: rs2043961707
Type: Deletion
Location: chr17:65537787 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 417: the 'disordered' region; the 'interaction with beta-catenin' 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.Ala417= Benign/Likely benign ★★ same residue
AXIN2 p.Ala417Val Benign/Likely benign ★★ same residue
AXIN2 p.Ala417Glu Uncertain significance ★ ⚠ same residue
AXIN2 p.Ala417Ser Uncertain significance ★ ⚠ same residue
AXIN2 p.Ala417Gly Likely benign ★ same residue
AXIN2 p.Ala492fs Pathogenic/Likely pathogenic ★★ same condition
AXIN2 p.Asn344fs Pathogenic ★★ same condition
AXIN2 p.Glu32fs 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-ala417fs (accessed [today's date]).

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