Is TMPO p.Leu5= (c.13C>T) pathogenic?

TMPO p.Leu5= (c.13C>T) is classified Benign/Likely benign in TMPO (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-08). Very rare (popmax 0.0067%, nfe); Associated with Loeys-Dietz syndrome 2.

What condition is associated with TMPO p.Leu5= (c.13C>T)?

TMPO p.Leu5= (c.13C>T) is associated with Loeys-Dietz syndrome 2 (ClinVar).

How common is TMPO p.Leu5= (c.13C>T) in the general population?

TMPO p.Leu5= (c.13C>T) is very rare (popmax 0.0067%, nfe) (gnomAD).

TMPO p.Leu5=

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.13C>T · rs149067616 · VCV695615

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0067%, nfe)

Conditions

Loeys-Dietz syndrome 2

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.22	GERP -0.48, phastCons 0.98
Overall
CADD	18.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0067% European (non-Finnish) · 79/1,179,710 alleles

Filtering AF 0.00546% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00506%

Overall 0.00508% 82/1,613,534 alleles · very rare exomes 74/1,461,186 · genomes 8/152,348 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0067%	14,933
Remaining individualsnot grpmax-eligible	0.0032%	31,236
African / African-American	0.00133%	75,032

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.Leu5=
Coding: c.13C>T
MANE Select: NM_001032283
dbSNP: rs149067616
Type: single nucleotide variant
Location: chr12:98515880 (GRCh38)

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

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-leu5 (accessed [today's date]).

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