Is AXIN2 p.Ser16Arg (c.48C>A) pathogenic?

AXIN2 p.Ser16Arg (c.48C>A) is classified Uncertain significance in AXIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-17). AlphaMissense: likely pathogenic (0.5778); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with AXIN2 p.Ser16Arg (c.48C>A)?

AXIN2 p.Ser16Arg (c.48C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is AXIN2 p.Ser16Arg (c.48C>A) in the general population?

AXIN2 p.Ser16Arg (c.48C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AXIN2 p.Ser16Arg (c.48C>A)?

AlphaMissense predicts likely pathogenic (score 0.5778) — an in-silico prediction, not a clinical call.

AXIN2 p.Ser16Arg

c.48C>A · VCV4619777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5778 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5778	likely pathogenic
REVEL	0.489	indeterminate
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP -0.9, phastCons 1
Regional constraint	o/e 0.14	constrained · MANE · 43 bp · p 8e-05 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AXIN2
Protein: p.Ser16Arg
Coding: c.48C>A
MANE Select: NM_004655
Type: single nucleotide variant
Location: chr17:65558573 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.71 · 1 PDB
Residue 16: 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.Ser16Gly Uncertain significance ★★ ⚠ same residue
AXIN2 p.Ser16= Benign/Likely benign ★★ same residue
AXIN2 p.Ser16Asn 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

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-ser16arg (accessed [today's date]).

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