Is AXIN2 p.Pro422= (c.1266C>G) pathogenic?

AXIN2 p.Pro422= (c.1266C>G) is classified Likely benign in AXIN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-06). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Pro422= (c.1266C>G)?

AXIN2 p.Pro422= (c.1266C>G) is associated with hereditary neoplastic syndrome, oligodontia-cancer predisposition syndrome (ClinVar).

How common is AXIN2 p.Pro422= (c.1266C>G) in the general population?

AXIN2 p.Pro422= (c.1266C>G) is absent from gnomAD v4.1 (gnomAD).

AXIN2 p.Pro422=

c.1266C>G · rs773785363 · VCV1120929

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,586,546)

Conditions

hereditary neoplastic 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 -0.057	GERP -1.4, phastCons 0.23
Overall
CADD	1.876	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,586,546). 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.Pro422=
Coding: c.1266C>G
MANE Select: NM_004655
dbSNP: rs773785363
Type: single nucleotide variant
Location: chr17:65537770 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 422: 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

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

Also linked: oligodontia-cancer predisposition syndrome

Similar variants

AXIN2 p.Pro422Ala Uncertain significance ★★ ⚠ same residue
AXIN2 p.Pro422Leu Uncertain significance ★★ ⚠ same residue
AXIN2 p.Pro422Ser Uncertain significance ★★ ⚠ same residue
AXIN2 p.Pro422Thr Uncertain significance ★★ ⚠ same residue
AXIN2 p.Pro422Arg 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-pro422 (accessed [today's date]).

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