Is AXIN2 p.Gln89Ter (c.265C>T) pathogenic?

AXIN2 p.Gln89Ter (c.265C>T) is classified Pathogenic in AXIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Gln89Ter (c.265C>T)?

AXIN2 p.Gln89Ter (c.265C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AXIN2 p.Gln89Ter (c.265C>T) in the general population?

AXIN2 p.Gln89Ter (c.265C>T) is absent from gnomAD v4.1 (gnomAD).

AXIN2 p.Gln89Ter

c.265C>T · VCV4188551

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

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.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 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	40.0	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

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.Gln89Ter
Coding: c.265C>T
MANE Select: NM_004655
Type: single nucleotide variant
Location: chr17:65558356 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 89: the rgs 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

Similar variants

AXIN2 p.Gln89His Uncertain significance ★★ ⚠ same residue
AXIN2 p.Gln89Lys Uncertain significance ★★ ⚠ same residue
AXIN2 p.Gln89Pro Uncertain significance ★★ ⚠ same residue
AXIN2 p.Gln89Arg Uncertain significance ★ ⚠ same residue
AXIN2 p.Gln89Glu Uncertain significance ★ ⚠ same residue
AXIN2 p.Gln89= Likely benign ★ 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-gln89ter (accessed [today's date]).

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