Is AXIN2 p.Ala783Pro (c.2347G>C) pathogenic?

AXIN2 p.Ala783Pro (c.2347G>C) is classified Uncertain significance in AXIN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-14). AlphaMissense: likely pathogenic (0.5758); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Ala783Pro (c.2347G>C)?

AXIN2 p.Ala783Pro (c.2347G>C) is associated with hereditary neoplastic syndrome, oligodontia-cancer predisposition syndrome (ClinVar).

How common is AXIN2 p.Ala783Pro (c.2347G>C) in the general population?

AXIN2 p.Ala783Pro (c.2347G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AXIN2 p.Ala783Pro (c.2347G>C)?

AlphaMissense predicts likely pathogenic (score 0.5758) — an in-silico prediction, not a clinical call.

AXIN2 p.Ala783Pro

c.2347G>C · rs760217787 · VCV567967

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5758 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5758	likely pathogenic
REVEL	0.249	benign-leaning
SaProt	LLR -10.06	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.2, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 4,033 bp · p 0.0017 · regional, not allelic
Overall
CADD	25.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AXIN2
Protein: p.Ala783Pro
Coding: c.2347G>C
MANE Select: NM_004655
dbSNP: rs760217787
Type: single nucleotide variant
Location: chr17:65533970 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 783: the dix domain

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.Ala783Gly Uncertain significance ★★ ⚠ same residue
AXIN2 p.Ala783Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
AXIN2 p.Ala783Val Uncertain significance ★ ⚠ same residue
AXIN2 p.Ala783_Gln784del 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-ala783pro (accessed [today's date]).

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