Is AXIN2 p.Asp843Val (c.2528A>T) pathogenic?

AXIN2 p.Asp843Val (c.2528A>T) is classified Uncertain significance in AXIN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-12). AlphaMissense: likely pathogenic (0.7303); Very rare (popmax 0.00333%, amr); Associated with oligodontia-cancer predisposition syndrome.

What condition is associated with AXIN2 p.Asp843Val (c.2528A>T)?

AXIN2 p.Asp843Val (c.2528A>T) is associated with oligodontia-cancer predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is AXIN2 p.Asp843Val (c.2528A>T) in the general population?

AXIN2 p.Asp843Val (c.2528A>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about AXIN2 p.Asp843Val (c.2528A>T)?

AlphaMissense predicts likely pathogenic (score 0.7303) — an in-silico prediction, not a clinical call.

AXIN2 p.Asp843Val

c.2528A>T · rs1413374885 · VCV2867491

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7303 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

oligodontia-cancer predisposition syndrome

Computational evidence

Protein change
AlphaMissense	0.7303	likely pathogenic
REVEL	0.571	indeterminate
SaProt	LLR -11.52	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 4,033 bp · p 0.0017 · regional, not allelic
Overall
CADD	27.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00333% Admixed American · 2/60,004 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,084 alleles · very rare

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.Asp843Val
Coding: c.2528A>T
MANE Select: NM_004655
dbSNP: rs1413374885
Type: single nucleotide variant
Location: chr17:65529980 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 843: the dix 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

Also linked: hereditary neoplastic syndrome

Similar variants

AXIN2 p.Asp843Asn Uncertain significance ★★ ⚠ same residue
AXIN2 p.Asp843His Uncertain significance ★★ ⚠ same residue
AXIN2 p.Asp843Tyr Uncertain significance ★★ ⚠ same residue
AXIN2 p.Asp843= Benign/Likely benign ★★ same residue
AXIN2 p.Asp843Gly 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-asp843val (accessed [today's date]).

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