Is AXIN2 p.Pro670= (c.2010C>T) pathogenic?

AXIN2 p.Pro670= (c.2010C>T) is classified Likely benign in AXIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-04). Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Pro670= (c.2010C>T)?

AXIN2 p.Pro670= (c.2010C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AXIN2 p.Pro670= (c.2010C>T) in the general population?

AXIN2 p.Pro670= (c.2010C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

AXIN2 p.Pro670=

c.2010C>T · rs781484593 · VCV2451665

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 2.8	GERP -0.08, phastCons 1
Overall
CADD	4.575	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Overall 6.2e-05% 1/1,613,642 alleles · very rare exomes 1/1,461,336 · genomes 0/152,306 · joint denominator

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.Pro670=
Coding: c.2010C>T
MANE Select: NM_004655
dbSNP: rs781484593
Type: single nucleotide variant
Location: chr17:65536451 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 670: 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.Pro670Arg Uncertain significance ★★ ⚠ same residue
AXIN2 p.Pro670Ser Uncertain significance ★★ ⚠ same residue
AXIN2 p.Pro670Thr Uncertain significance ★★ ⚠ same residue
AXIN2 p.Pro670Ala Uncertain significance ★ ⚠ same residue
AXIN2 p.Pro670Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
AXIN2 p.Pro670fs Pathogenic ★ same residue
AXIN2 p.Pro670His Uncertain significance ★ ⚠ same residue
AXIN2 c.1060-1G>C 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-pro670 (accessed [today's date]).

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