Is AXIN2 p.Asp320Val (c.959A>T) pathogenic?

AXIN2 p.Asp320Val (c.959A>T) is classified Uncertain significance in AXIN2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-18). AlphaMissense: likely pathogenic (0.9278); Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Asp320Val (c.959A>T)?

AXIN2 p.Asp320Val (c.959A>T) is associated with hereditary neoplastic syndrome, oligodontia-cancer predisposition syndrome (ClinVar).

How common is AXIN2 p.Asp320Val (c.959A>T) in the general population?

AXIN2 p.Asp320Val (c.959A>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about AXIN2 p.Asp320Val (c.959A>T)?

AlphaMissense predicts likely pathogenic (score 0.9278) — an in-silico prediction, not a clinical call.

AXIN2 p.Asp320Val

c.959A>T · rs1462955225 · VCV647987

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9278 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9278	likely pathogenic · top 10% in AXIN2
REVEL	0.832	moderately pathogenic-leaning
SaProt	LLR -6.18	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 25 kb · p 0.011 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Overall 6.85e-05% 1/1,460,654 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.Asp320Val
Coding: c.959A>T
MANE Select: NM_004655
dbSNP: rs1462955225
Type: single nucleotide variant
Location: chr17:65541555 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: oligodontia-cancer predisposition syndrome

Similar variants

AXIN2 p.Asp320His Uncertain significance ★★ ⚠ same residue
AXIN2 p.Asp320= Likely benign ★★ same residue
AXIN2 p.Asp320Asn Uncertain significance ★ ⚠ same residue
AXIN2 p.Asp320Gly 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
AXIN2 c.1713-1G>A 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-asp320val (accessed [today's date]).

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