Is TBP p.Pro151Ser (c.451C>T) pathogenic?

TBP p.Pro151Ser (c.451C>T) is classified Uncertain significance in TBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely pathogenic (0.9146); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TBP p.Pro151Ser (c.451C>T)?

TBP p.Pro151Ser (c.451C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TBP p.Pro151Ser (c.451C>T) in the general population?

TBP p.Pro151Ser (c.451C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TBP p.Pro151Ser (c.451C>T)?

AlphaMissense predicts likely pathogenic (score 0.9146) — an in-silico prediction, not a clinical call.

TBP p.Pro151Ser

c.451C>T · VCV3966178

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9146 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9146	likely pathogenic
REVEL	0.242	benign-leaning
SaProt	LLR -9.97	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 9,277 bp · p 1e-18 · regional, not allelic
Overall
CADD	23.0	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: TBP
Protein: p.Pro151Ser
Coding: c.451C>T
MANE Select: NM_003194
Type: single nucleotide variant
Location: chr6:170562187 (GRCh38)
Gene constraint: LOEUF 0.41 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.28 · 81 PDB
Residue 151: the 'disordered' region

Full TBP 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

Similar variants

TBP p.Pro133Leu Uncertain significance ★★ ⚠ same condition
TBP p.Pro137Leu Uncertain significance ★★ ⚠ same condition
TBP p.Gln72= Benign/Likely benign ★★ same condition
TBP p.Ala11Thr Uncertain significance ★ ⚠ same condition
TBP p.Ala155Gly Uncertain significance ★ ⚠ same condition
TBP p.Ala184Val Uncertain significance ★ ⚠ same condition
TBP p.Ala96Thr Uncertain significance ★ ⚠ same condition
TBP p.Arg186His 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/tbp-p-pro151ser (accessed [today's date]).

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