Is TMPO p.Ala29Val (c.86C>T) pathogenic?

TMPO p.Ala29Val (c.86C>T) is classified Uncertain significance in TMPO (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-13). AlphaMissense: likely benign (0.0987); Absent from gnomAD v4.1; Associated with TMPO-related disorder.

What condition is associated with TMPO p.Ala29Val (c.86C>T)?

TMPO p.Ala29Val (c.86C>T) is associated with TMPO-related disorder (ClinVar).

How common is TMPO p.Ala29Val (c.86C>T) in the general population?

TMPO p.Ala29Val (c.86C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TMPO p.Ala29Val (c.86C>T)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

TMPO p.Ala29Val

c.86C>T · VCV3358074

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

TMPO-related disorder

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -7.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -0.077, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 28 kb · p 0.89 · regional, not allelic
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TMPO
Protein: p.Ala29Val
Coding: c.86C>T
MANE Select: NM_001032283
Type: single nucleotide variant
Location: chr12:98515953 (GRCh38)
Gene constraint: LOEUF 0.736 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.49 · 14 PDB
Residue 29: the lem-like domain; a β-strand; the 'nucleoplasmic' region

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

Disease context

TMPO-related disorder

Similar variants

TMPO p.Ala29Thr Uncertain significance ★★ ⚠ same residue
TMPO p.Ala29= Benign/Likely benign ★★ same residue
TMPO p.Ala29Ser Uncertain significance ★ ⚠ same residue
TMPO c.565+2300T>A Uncertain significance ★ same condition
TMPO p.Ala433Thr Uncertain significance same condition
TMPO p.Asp399Gly Uncertain significance same condition
TMPO p.Pro242Leu Uncertain significance same condition
TMPO c.565+1005A>G 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-ala29val (accessed [today's date]).

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