Is AXIN1 p.Ser579Pro (c.1735T>C) pathogenic?

AXIN1 p.Ser579Pro (c.1735T>C) is classified Uncertain significance in AXIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.0756); Very rare (popmax 0.00269%, afr).

How common is AXIN1 p.Ser579Pro (c.1735T>C) in the general population?

AXIN1 p.Ser579Pro (c.1735T>C) is very rare (popmax 0.00269%, afr) (gnomAD).

What do computational predictors say about AXIN1 p.Ser579Pro (c.1735T>C)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

AXIN1 p.Ser579Pro

c.1735T>C · rs2052754946 · VCV3132476

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.49	GERP -3.1, phastCons 0.003
Regional constraint	o/e 1.06	unconstrained · MANE · 9,666 bp · p 0.25 · regional, not allelic
Overall
CADD	6.021	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 0.00269% African / African-American · 2/74,344 alleles

Filtering AF 0.000446% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000252% 4/1,584,742 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,172
Admixed American	0.00174%	57,316
Remaining individualsnot grpmax-eligible	0.00164%	61,154

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.Ser579Pro
Coding: c.1735T>C
MANE Select: NM_003502
dbSNP: rs2052754946
Type: single nucleotide variant
Location: chr16:297771 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI 0.16 (gnomAD)
Structure: AlphaFold pLDDT 62.32 · 22 PDB
Residue 579: the 'interaction with rnf111' region; the 'disordered' region; the 'interaction with ppp2ca' region

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-ser579pro (accessed [today's date]).

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