Is AXIN2 p.Ala306Val (c.917C>T) pathogenic?

AXIN2 p.Ala306Val (c.917C>T) is classified Uncertain significance in AXIN2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-04-15). AlphaMissense: likely benign (0.2831); Ultra-rare (popmax 0.012%, afr); Associated with colorectal cancer.

What condition is associated with AXIN2 p.Ala306Val (c.917C>T)?

AXIN2 p.Ala306Val (c.917C>T) is associated with colorectal cancer, oligodontia-cancer predisposition syndrome, hereditary neoplastic syndrome (ClinVar).

How common is AXIN2 p.Ala306Val (c.917C>T) in the general population?

AXIN2 p.Ala306Val (c.917C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about AXIN2 p.Ala306Val (c.917C>T)?

AlphaMissense predicts likely benign (score 0.2831) — an in-silico prediction, not a clinical call.

AXIN2 p.Ala306Val

c.917C>T · rs151247101 · VCV240040

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2831 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

colorectal cancer

Computational evidence

Protein change
AlphaMissense	0.2831	likely benign
REVEL	0.568	indeterminate
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2.1, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 25 kb · p 0.011 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,978 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00137% 22/1,611,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,331
East Asian	0.00447%	22,373
Admixed American	0.00168%	59,606
European (non-Finnish)	0.000848%	117,866

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.Ala306Val
Coding: c.917C>T
MANE Select: NM_004655
dbSNP: rs151247101
Type: single nucleotide variant
Location: chr17:65549559 (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

colorectal cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: oligodontia-cancer predisposition syndrome hereditary neoplastic syndrome

Similar variants

AXIN2 p.Ala306Gly Uncertain significance ★★ ⚠ same residue
AXIN2 p.Ala306= Benign/Likely benign ★★ same residue
AXIN2 p.Ala306Glu Uncertain significance ★ same residue
AXIN2 p.Ala306Thr 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

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-ala306val (accessed [today's date]).

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