Is AXIN1 p.Ile855= (c.2565C>T) pathogenic?

AXIN1 p.Ile855= (c.2565C>T) is classified Benign/Likely benign in AXIN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-01). Rare (popmax 0.132%, mid).

How common is AXIN1 p.Ile855= (c.2565C>T) in the general population?

AXIN1 p.Ile855= (c.2565C>T) is rare (popmax 0.132%, mid) (gnomAD).

AXIN1 p.Ile855=

c.2565C>T · rs150808160 · VCV721381

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

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 -3.5	GERP -3.4
Overall
CADD	0.581	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% Middle Eastern · 8/6,062 alleles

Filtering AF 0.0656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.056% 903/1,613,504 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.331%	302
Finnishnot grpmax-eligible	0.284%	352
Middle Easterngrpmax	0.132%	758
Amishnot grpmax-eligible	0.11%	912
Remaining individualsnot grpmax-eligible	0.0784%	1,276
European (non-Finnish)	0.0454%	2,201
Admixed American	0.0217%	4,617
South Asian	0.0154%	6,506
African / African-American	0.004%	25,015
East Asian	0.00223%	44,878

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: AXIN1
Protein: p.Ile855=
Coding: c.2565C>T
MANE Select: NM_003502
dbSNP: rs150808160
Type: single nucleotide variant
Location: chr16:288146 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI 0.16 (gnomAD)
Structure: AlphaFold pLDDT 62.32 · 22 PDB
Residue 855: the dix domain; a UniProt-annotated variant site (in cmdoh; likely pathogenic; loss of negative regulation of canonical wnt signaling pathway; results in enhanced basal wnt signaling in primary homozygous patient-derived fibroblasts and in genome-edited cells; the mutant protein is expressed at low levels in primary homozygous patient-derived fibroblasts); a UniProt-annotated variant site (in cmdoh; uncertain significance); a β-strand

Full AXIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AXIN1 p.Arg373His Uncertain significance ★★ ⚠ same type
AXIN1 c.2186+4C>T Likely benign ★★ same type
AXIN1 c.2186+7C>T Benign/Likely benign ★★ same type
AXIN1 p.Ala526Val Benign ★★ ⚠ same type
AXIN1 p.Ala552= Benign ★★ same type
AXIN1 p.Arg801= Benign/Likely benign ★★ same type
AXIN1 p.Arg803= Benign ★★ same type
AXIN1 p.Arg841Gln Benign/Likely benign ★★ ⚠ same type

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/axin1-p-ile855 (accessed [today's date]).

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