Is TMPO p.Asn178= (c.534T>C) pathogenic?

TMPO p.Asn178= (c.534T>C) is classified Benign/Likely benign in TMPO (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-06-08). Ultra-rare (popmax 0.0335%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TMPO p.Asn178= (c.534T>C)?

TMPO p.Asn178= (c.534T>C) is associated with Inborn genetic diseases, Loeys-Dietz syndrome 2 (ClinVar).

How common is TMPO p.Asn178= (c.534T>C) in the general population?

TMPO p.Asn178= (c.534T>C) is ultra-rare (popmax 0.0335%, nfe) (gnomAD).

TMPO p.Asn178=

c.534T>C · rs200016687 · VCV44672

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, nfe)

Conditions

Inborn genetic diseases

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 -0.48	GERP -5, phastCons 0.14
Overall
CADD	6.299	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0335% European (non-Finnish) · 395/1,179,858 alleles

Filtering AF 0.0307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.0249% 402/1,613,622 alleles · ultra-rare exomes 378/1,461,436 · genomes 24/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0335%	2,987
Remaining individualsnot grpmax-eligible	0.00801%	12,492
Finnishnot grpmax-eligible	0.00156%	64,026
African / African-American	0.00134%	74,894

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.Asn178=
Coding: c.534T>C
MANE Select: NM_001032283
dbSNP: rs200016687
Type: single nucleotide variant
Location: chr12:98531807 (GRCh38)
Gene constraint: LOEUF 0.736 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.49 · 14 PDB
Residue 178: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Loeys-Dietz syndrome 2

Similar variants

TMPO c.565+1005A>G Uncertain significance ★★ ⚠ same condition
TMPO c.565+1009T>C Uncertain significance ★★ ⚠ same condition
TMPO c.565+1012A>C Uncertain significance ★★ ⚠ same condition
TMPO c.565+1017A>G Uncertain significance ★★ ⚠ same condition
TMPO c.565+1026A>G Uncertain significance ★★ ⚠ same condition
TMPO c.565+1029G>T Uncertain significance ★★ ⚠ same condition
TMPO c.565+1048G>C Uncertain significance ★★ ⚠ same condition
TMPO c.565+1053A>G 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-asn178 (accessed [today's date]).

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