Is AXIN2 p.Glu627Ter (c.1879G>T) pathogenic?

AXIN2 p.Glu627Ter (c.1879G>T) is classified Conflicting classifications of pathogenicity in AXIN2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-05-20). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Glu627Ter (c.1879G>T)?

AXIN2 p.Glu627Ter (c.1879G>T) is associated with hereditary neoplastic syndrome, oligodontia-cancer predisposition syndrome (ClinVar).

How common is AXIN2 p.Glu627Ter (c.1879G>T) in the general population?

AXIN2 p.Glu627Ter (c.1879G>T) is absent from gnomAD v4.1 (gnomAD).

AXIN2 p.Glu627Ter

c.1879G>T · rs1598097733 · VCV1781848

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,560)

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 7 of 11
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.36	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3.8	GERP 1.7, phastCons 1
Overall
CADD	42.0	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

No allele count reported in gnomAD v4.1 (AN 1,613,560). 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.Glu627Ter
Coding: c.1879G>T
MANE Select: NM_004655
dbSNP: rs1598097733
Type: single nucleotide variant
Location: chr17:65536897 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 627: 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

Also linked: oligodontia-cancer predisposition syndrome

Similar variants

AXIN2 p.Glu627Lys Uncertain significance ★★ ⚠ same residue
AXIN2 p.Glu627= Likely benign ★ 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-glu627ter (accessed [today's date]).

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