Is AXIN2 p.Pro50Phe (c.148_149delinsTT) pathogenic?

AXIN2 p.Pro50Phe (c.148149delinsTT) is classified Uncertain significance in AXIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-19). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Pro50Phe (c.148_149delinsTT)?

AXIN2 p.Pro50Phe (c.148_149delinsTT) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AXIN2 p.Pro50Phe (c.148_149delinsTT) in the general population?

AXIN2 p.Pro50Phe (c.148_149delinsTT) is absent from gnomAD (gnomAD).

AXIN2 p.Pro50Phe

c.148_149delinsTT · rs2544254629 · VCV1773553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 8.5	GERP 0.095, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 25 kb · p 0.011 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AXIN2
Protein: p.Pro50Phe
Coding: c.148_149delinsTT
MANE Select: NM_004655
dbSNP: rs2544254629
Type: Indel
Location: chr17:65558472 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 50: a UniProt-annotated variant site (in); the 'disordered' 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

Similar variants

AXIN2 p.Pro50Ser Benign ★★ same residue
AXIN2 p.Pro50Arg Uncertain significance ★ ⚠ same residue
AXIN2 p.Pro50= Likely benign ★ same residue
AXIN2 p.Pro50Thr Likely benign ★ same residue
AXIN2 p.Gly665fs Pathogenic ★★ same condition
AXIN2 p.Ala599Asn Uncertain significance ★★ same condition
AXIN2 p.Arg671_Arg675delinsCys Uncertain significance ★★ same condition
AXIN2 p.Ile775Phe Uncertain significance ★★ 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-pro50phe (accessed [today's date]).

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