Is TMPO p.Pro28fs (c.80dup) pathogenic?

TMPO p.Pro28fs (c.80dup) is classified Uncertain significance in TMPO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-17). No gnomAD frequency available for this variant.

How common is TMPO p.Pro28fs (c.80dup) in the general population?

TMPO p.Pro28fs (c.80dup) is no gnomAD frequency available for this variant (gnomAD).

TMPO p.Pro28fs

c.80dup · rs2548488744 · VCV2572875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.5	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TMPO
Protein: p.Pro28fs
Coding: c.80dup
MANE Select: NM_001032283
dbSNP: rs2548488744
Type: Duplication
Location: chr12:98515946 (GRCh38)
Gene constraint: LOEUF 0.736 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.49 · 14 PDB
Residue 28: the lem-like domain; the 'nucleoplasmic' region

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

Similar variants

TMPO p.Pro28= Likely benign ★★ same residue
TMPO p.Pro28Leu Uncertain significance ★ ⚠ same residue
TMPO c.565+1488dup Uncertain significance ★★ same type
TMPO c.565+1664dup Uncertain significance ★★ same type
TMPO c.1079+5dup Benign ★★ same type
TMPO c.565+1829dup Uncertain significance ★ same type
TMPO c.565+2173dup Uncertain significance ★ same type
TMPO p.Tyr223_Ser224insTyr 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/tmpo-p-pro28fs (accessed [today's date]).

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