Is TMPO p.Asp179Glu (c.537T>A) pathogenic?

TMPO p.Asp179Glu (c.537T>A) is classified Uncertain significance in TMPO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-02). AlphaMissense: likely pathogenic (0.8473); Absent from gnomAD v4.1.

How common is TMPO p.Asp179Glu (c.537T>A) in the general population?

TMPO p.Asp179Glu (c.537T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TMPO p.Asp179Glu (c.537T>A)?

AlphaMissense predicts likely pathogenic (score 0.8473) — an in-silico prediction, not a clinical call.

TMPO p.Asp179Glu

c.537T>A · VCV3327282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8473 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8473	likely pathogenic · top 10% in TMPO
REVEL	0.29	benign-leaning
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.41	GERP -0.078, phastCons 0.99
Regional constraint	o/e 1.01	unconstrained · MANE · 28 kb · p 0.89 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

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.Asp179Glu
Coding: c.537T>A
MANE Select: NM_001032283
Type: single nucleotide variant
Location: chr12:98531810 (GRCh38)
Gene constraint: LOEUF 0.736 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.49 · 14 PDB
Residue 179: 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

Similar variants

TMPO p.Asp179Asn 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
TMPO c.565+1048G>C 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-asp179glu (accessed [today's date]).

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