Is TMPO p.Thr160del (c.478_480del) pathogenic?

TMPO p.Thr160del (c.478480del) is classified Uncertain significance in TMPO (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-22). Very rare (popmax 0.00167%, amr); Associated with Loeys-Dietz syndrome 2.

What condition is associated with TMPO p.Thr160del (c.478_480del)?

TMPO p.Thr160del (c.478_480del) is associated with Loeys-Dietz syndrome 2 (ClinVar).

How common is TMPO p.Thr160del (c.478_480del) in the general population?

TMPO p.Thr160del (c.478_480del) is very rare (popmax 0.00167%, amr) (gnomAD).

TMPO p.Thr160del

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.478_480del · rs2548501750 · VCV2031834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Loeys-Dietz syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 2.5, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,010 alleles

Overall 6.2e-05% 1/1,613,792 alleles · very rare exomes 1/1,461,502 · genomes 0/152,290 · joint denominator

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: TMPO
Protein: p.Thr160del
Coding: c.478_480del
MANE Select: NM_001032283
dbSNP: rs2548501750
Type: Deletion
Location: chr12:98531749 (GRCh38)
Gene constraint: LOEUF 0.736 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.49 · 14 PDB
Residue 160: a modified residue (phosphothreonine); the 'disordered' region; the 'nakap95-binding n' region; the 'nucleoplasmic' region

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

Disease context

Loeys-Dietz syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

TMPO p.Thr160Ile Uncertain significance ★★ ⚠ same residue
TMPO p.Thr160Pro Uncertain significance ★ ⚠ same residue
TMPO c.565+1536_565+1543del Uncertain significance ★★ same condition
TMPO c.565+1928del Uncertain significance ★★ same condition
TMPO c.565+1983del Uncertain significance ★★ same condition
TMPO c.565+2304del Uncertain significance ★★ same condition
TMPO c.565+1272del Uncertain significance ★ same condition
TMPO c.565+1350_565+1352del Uncertain significance ★ 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/tmpo-p-thr160del (accessed [today's date]).

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