Is AXIN2 p.Ser428= (c.1284C>G) pathogenic?

AXIN2 p.Ser428= (c.1284C>G) is classified Likely benign in AXIN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-26). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Ser428= (c.1284C>G)?

AXIN2 p.Ser428= (c.1284C>G) is associated with hereditary neoplastic syndrome, oligodontia-cancer predisposition syndrome (ClinVar).

How common is AXIN2 p.Ser428= (c.1284C>G) in the general population?

AXIN2 p.Ser428= (c.1284C>G) is absent from gnomAD v4.1 (gnomAD).

AXIN2 p.Ser428=

c.1284C>G · VCV3980804

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.37 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.5	GERP -3.7
Overall
CADD	0.297	PHRED · no single calibrated threshold — expert panels disagree

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.Ser428=
Coding: c.1284C>G
MANE Select: NM_004655
Type: single nucleotide variant
Location: chr17:65537752 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 428: 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.Ser428Cys Uncertain significance ★★ ⚠ same residue
AXIN2 p.Ser428Phe Uncertain significance ★★ ⚠ same residue
AXIN2 p.Ser428Pro Uncertain significance ★★ ⚠ same residue
AXIN2 p.Ser428Ala Uncertain significance ★ ⚠ same residue
AXIN2 p.Ser428Tyr Uncertain significance ★ ⚠ same residue
AXIN2 p.Ser428fs Pathogenic ★ same residue
AXIN2 c.1060-1G>C Likely pathogenic ★★ same condition
AXIN2 c.1200+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-ser428 (accessed [today's date]).

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