Is TPX2 p.Pro13Arg (c.38C>G) pathogenic?

TPX2 p.Pro13Arg (c.38C>G) is classified Uncertain significance in TPX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: ambiguous (0.4109); Very rare (popmax 0.000169%, nfe).

How common is TPX2 p.Pro13Arg (c.38C>G) in the general population?

TPX2 p.Pro13Arg (c.38C>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about TPX2 p.Pro13Arg (c.38C>G)?

AlphaMissense predicts ambiguous (score 0.4109) — an in-silico prediction, not a clinical call.

TPX2 p.Pro13Arg

c.38C>G · VCV3460636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4109 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4109	ambiguous
REVEL	0.565	indeterminate
SaProt	LLR -6.98	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2.7, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 2,633 bp · p 0.0035 · regional, not allelic
Overall
CADD	23.8	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

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,998 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,798 alleles · very rare

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: TPX2
Protein: p.Pro13Arg
Coding: c.38C>G
MANE Select: NM_012112
Type: single nucleotide variant
Location: chr20:31757514 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.23 · 14 PDB

Full TPX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TPX2 p.Ala184= Benign ★★ same type
TPX2 p.Ser94= Benign ★★ same type
TPX2 p.Ala142Val Uncertain significance ★ ⚠ same type
TPX2 p.Ala184Gly Uncertain significance ★ ⚠ same type
TPX2 p.Ala668Val Uncertain significance ★ same type
TPX2 p.Ala683Pro Uncertain significance ★ ⚠ same type
TPX2 p.Arg229Trp Uncertain significance ★ ⚠ same type
TPX2 p.Arg267Gln Uncertain significance ★ ⚠ 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/tpx2-p-pro13arg (accessed [today's date]).

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