Is AXIN2 p.Ala417Glu (c.1250C>A) pathogenic?

AXIN2 p.Ala417Glu (c.1250C>A) is classified Uncertain significance in AXIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-06). AlphaMissense: likely benign (0.1128); Absent from gnomAD v4.1; Associated with oligodontia-cancer predisposition syndrome.

What condition is associated with AXIN2 p.Ala417Glu (c.1250C>A)?

AXIN2 p.Ala417Glu (c.1250C>A) is associated with oligodontia-cancer predisposition syndrome (ClinVar).

How common is AXIN2 p.Ala417Glu (c.1250C>A) in the general population?

AXIN2 p.Ala417Glu (c.1250C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AXIN2 p.Ala417Glu (c.1250C>A)?

AlphaMissense predicts likely benign (score 0.1128) — an in-silico prediction, not a clinical call.

AXIN2 p.Ala417Glu

c.1250C>A · rs201460658 · VCV2693588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1128 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,586,632)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oligodontia-cancer predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.1128	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -6.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.072	GERP -1.5
Regional constraint	o/e 1.08	unconstrained · MANE · 25 kb · p 0.011 · regional, not allelic
Overall
CADD	6.733	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,586,632). 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.Ala417Glu
Coding: c.1250C>A
MANE Select: NM_004655
dbSNP: rs201460658
Type: single nucleotide variant
Location: chr17:65537786 (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

Similar variants

AXIN2 p.Ala417= Benign/Likely benign ★★ same residue
AXIN2 p.Ala417Val Benign/Likely benign ★★ same residue
AXIN2 p.Ala417fs Pathogenic ★★ same residue
AXIN2 p.Ala417Ser Uncertain significance ★ ⚠ same residue
AXIN2 p.Ala417Gly Likely benign ★ 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

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-ala417glu (accessed [today's date]).

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