Is AXIN2 p.Gln638= (c.1914A>G) pathogenic?

AXIN2 p.Gln638= (c.1914A>G) is classified Likely benign in AXIN2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-10). Very rare (popmax 0.000137%); Associated with oligodontia-cancer predisposition syndrome.

What condition is associated with AXIN2 p.Gln638= (c.1914A>G)?

AXIN2 p.Gln638= (c.1914A>G) is associated with oligodontia-cancer predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is AXIN2 p.Gln638= (c.1914A>G) in the general population?

AXIN2 p.Gln638= (c.1914A>G) is very rare (popmax 0.000137%) (gnomAD).

AXIN2 p.Gln638=

c.1914A>G · rs1282533521 · VCV839072

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000137%)

Conditions

oligodontia-cancer predisposition 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 -0.35	GERP -2.5, phastCons 0.092
Overall
CADD	4.471	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000137%

Overall 0.000137% 2/1,461,400 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.Gln638=
Coding: c.1914A>G
MANE Select: NM_004655
dbSNP: rs1282533521
Type: single nucleotide variant
Location: chr17:65536547 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 638: the 'disordered' region

Full AXIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

oligodontia-cancer predisposition syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

Similar variants

AXIN2 p.Gln638Ter Pathogenic ★★ same residue
AXIN2 p.Gln638Glu 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
AXIN2 c.816-1G>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-gln638 (accessed [today's date]).

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