Is AXIN2 p.Gln696Ter (c.2086C>T) pathogenic?

AXIN2 p.Gln696Ter (c.2086C>T) is classified Pathogenic in AXIN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-26). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Gln696Ter (c.2086C>T)?

AXIN2 p.Gln696Ter (c.2086C>T) is associated with hereditary neoplastic syndrome, oligodontia-cancer predisposition syndrome, AXIN2-related attenuated familial adenomatous polyposis (ClinVar).

How common is AXIN2 p.Gln696Ter (c.2086C>T) in the general population?

AXIN2 p.Gln696Ter (c.2086C>T) is absent from gnomAD v4.1 (gnomAD).

AXIN2 p.Gln696Ter

c.2086C>T · rs2043915274 · VCV1027575

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 8 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Overall
CADD	52.0	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.Gln696Ter
Coding: c.2086C>T
MANE Select: NM_004655
dbSNP: rs2043915274
Type: single nucleotide variant
Location: chr17:65536375 (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 AXIN2-related attenuated familial adenomatous polyposis

Similar variants

AXIN2 p.Gln696Arg Uncertain significance ★★ ⚠ same residue
AXIN2 p.Gln696Glu Uncertain significance ★ ⚠ same residue
AXIN2 p.Gln696_Arg703delinsLeu 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
AXIN2 c.1713-1G>A Likely pathogenic ★★ same condition
AXIN2 c.815+1G>A Pathogenic/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-gln696ter (accessed [today's date]).

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