Is TPX2 p.Ala184= (c.552A>G) pathogenic?

TPX2 p.Ala184= (c.552A>G) is classified Benign in TPX2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-04-04). Common (popmax 7.19%, afr) — too common for a highly-penetrant pathogenic allele.

TPX2 p.Ala184=

Q: How common is TPX2 p.Ala184= (c.552A>G) in the general population?

TPX2 p.Ala184= (c.552A>G) is common (popmax 7.19%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.552A>G · rs58399677 · VCV775646

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.19%, afr) — too common for a highly-penetrant pathogenic allele

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 0.14	GERP -3.3, phastCons 0.009
Overall
CADD	6.226	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.19% African / African-American · 5,392/74,990 alleles

Filtering AF 7.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.96%

Overall 0.41% 6,618/1,613,932 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.19%	14
Remaining individualsnot grpmax-eligible	0.65%	154
Admixed American	0.572%	175
Middle Eastern	0.561%	178
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,466
European (non-Finnish)	0.0351%	2,850
South Asian	0.0143%	7,004
Finnishnot grpmax-eligible	0.00625%	16,008

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.Ala184=
Coding: c.552A>G
MANE Select: NM_012112
dbSNP: rs58399677
Type: single nucleotide variant
Location: chr20:31771626 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.23 · 14 PDB
Residue 184: the 'disordered' region

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

Similar variants

TPX2 p.Ala184Gly Uncertain significance ★ ⚠ same residue
TPX2 p.Ser94= Benign ★★ same type
TPX2 p.Ala142Val 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
TPX2 p.Arg296Gln 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-ala184 (accessed [today's date]).

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