Is AXIN2 p.Ser260= (c.780T>C) pathogenic?

AXIN2 p.Ser260= (c.780T>C) is classified Benign/Likely benign in AXIN2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0344%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Ser260= (c.780T>C)?

AXIN2 p.Ser260= (c.780T>C) is associated with hereditary neoplastic syndrome, oligodontia-cancer predisposition syndrome (ClinVar).

How common is AXIN2 p.Ser260= (c.780T>C) in the general population?

AXIN2 p.Ser260= (c.780T>C) is ultra-rare (popmax 0.0344%, nfe) (gnomAD).

AXIN2 p.Ser260=

c.780T>C · rs147681058 · VCV240030

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0344%, nfe)

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 -2.4	GERP -3.9
Overall
CADD	0.752	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0344% European (non-Finnish) · 406/1,180,032 alleles

Filtering AF 0.0316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0305%

Overall 0.0261% 422/1,613,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0344%	2,906
Remaining individualsnot grpmax-eligible	0.0112%	8,926
African / African-American	0.00668%	14,976
Finnishnot grpmax-eligible	0.00625%	16,005

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.Ser260=
Coding: c.780T>C
MANE Select: NM_004655
dbSNP: rs147681058
Type: single nucleotide variant
Location: chr17:65557841 (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.Ser260Ile Uncertain significance ★★ ⚠ same residue
AXIN2 p.Ser260Cys Uncertain significance ★ ⚠ same residue
AXIN2 p.Ser260Thr Uncertain significance ★ ⚠ same residue
AXIN2 p.Ser260Asn Likely benign ★ 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-ser260 (accessed [today's date]).

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