Is TMPO p.Ser66= (c.198C>T) pathogenic?

TMPO p.Ser66= (c.198C>T) is classified Likely benign in TMPO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-07). Very rare (popmax 6.22e-05%).

How common is TMPO p.Ser66= (c.198C>T) in the general population?

TMPO p.Ser66= (c.198C>T) is very rare (popmax 6.22e-05%) (gnomAD).

TMPO p.Ser66=

c.198C>T · rs1875767643 · VCV2625259

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.22e-05%)

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 0.92	GERP -0.22, phastCons 1
Overall
CADD	18.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.22e-05%

Overall 6.22e-05% 1/1,608,630 alleles · very rare exomes 1/1,456,354 · genomes 0/152,276 · 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.Ser66=
Coding: c.198C>T
MANE Select: NM_001032283
dbSNP: rs1875767643
Type: single nucleotide variant
Location: chr12:98516065 (GRCh38)
Gene constraint: LOEUF 0.736 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.49 · 14 PDB
Residue 66: a modified residue (phosphoserine); the 'disordered' region; the 'linker' region; the 'nucleoplasmic' region

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

Similar variants

TMPO p.Ser66Phe Uncertain significance ★ ⚠ same residue
TMPO p.Ser66Tyr Uncertain significance ★ ⚠ same residue
TMPO c.565+1005A>G Uncertain significance ★★ ⚠ same type
TMPO c.565+1009T>C Uncertain significance ★★ ⚠ same type
TMPO c.565+1012A>C Uncertain significance ★★ ⚠ same type
TMPO c.565+1017A>G Uncertain significance ★★ ⚠ same type
TMPO c.565+1026A>G Uncertain significance ★★ ⚠ same type
TMPO c.565+1029G>T 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-ser66 (accessed [today's date]).

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