Is AXIN2 p.Asp299= (c.897C>T) pathogenic?

AXIN2 p.Asp299= (c.897C>T) is classified Conflicting classifications of pathogenicity in AXIN2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-09). Very rare (popmax 0.00297%, nfe); Associated with oligodontia-cancer predisposition syndrome.

What condition is associated with AXIN2 p.Asp299= (c.897C>T)?

AXIN2 p.Asp299= (c.897C>T) is associated with oligodontia-cancer predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is AXIN2 p.Asp299= (c.897C>T) in the general population?

AXIN2 p.Asp299= (c.897C>T) is very rare (popmax 0.00297%, nfe) (gnomAD).

AXIN2 p.Asp299=

c.897C>T · rs748143308 · VCV324651

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

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 1.7	GERP -0.039, phastCons 1
Overall
CADD	7.448	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00297% European (non-Finnish) · 35/1,177,772 alleles

Filtering AF 0.00216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00236% 38/1,609,258 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00297%	33,651
Admixed American	0.00169%	59,342
Remaining individualsnot grpmax-eligible	0.0016%	62,340
African / African-American	0.00134%	74,870

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.Asp299=
Coding: c.897C>T
MANE Select: NM_004655
dbSNP: rs748143308
Type: single nucleotide variant
Location: chr17:65549579 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB

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.Asp299Asn Uncertain significance ★★ ⚠ same residue
AXIN2 p.Asp299Ala Uncertain significance ★ ⚠ same residue
AXIN2 p.Asp299Glu Uncertain significance ★ ⚠ same residue
AXIN2 p.Asp299Gly Uncertain significance ★ ⚠ same residue
AXIN2 p.Asp299Tyr 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

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-asp299 (accessed [today's date]).

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