Is AXIN2 p.Gln760Ter (c.2278C>T) pathogenic?

AXIN2 p.Gln760Ter (c.2278C>T) is classified Pathogenic/Likely pathogenic in AXIN2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-03). Very rare (popmax 8.47e-05%, nfe); Associated with AXIN2-related disorder.

What condition is associated with AXIN2 p.Gln760Ter (c.2278C>T)?

AXIN2 p.Gln760Ter (c.2278C>T) is associated with AXIN2-related disorder, oligodontia-cancer predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is AXIN2 p.Gln760Ter (c.2278C>T) in the general population?

AXIN2 p.Gln760Ter (c.2278C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

AXIN2 p.Gln760Ter

c.2278C>T · rs752865337 · VCV2085310

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

AXIN2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Overall
CADD	50.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,044 alleles

Overall 6.84e-05% 1/1,461,890 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.Gln760Ter
Coding: c.2278C>T
MANE Select: NM_004655
dbSNP: rs752865337
Type: single nucleotide variant
Location: chr17:65534039 (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

AXIN2-related disorder

Also linked: oligodontia-cancer predisposition syndrome hereditary neoplastic syndrome

Similar variants

AXIN2 p.Gln760= Benign/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
AXIN2 c.815+1G>A Pathogenic/Likely pathogenic ★★ same condition
AXIN2 c.816-1G>A Likely pathogenic ★★ same condition
AXIN2 p.Arg129Ter 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-gln760ter (accessed [today's date]).

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