Is TBX1 p.Pro57Ser (c.169C>T) pathogenic?

TBX1 p.Pro57Ser (c.169C>T) is classified Uncertain significance in TBX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-17). AlphaMissense: likely benign (0.0708); Absent from gnomAD v4.1; Associated with DiGeorge syndrome.

What condition is associated with TBX1 p.Pro57Ser (c.169C>T)?

TBX1 p.Pro57Ser (c.169C>T) is associated with DiGeorge syndrome (ClinVar).

How common is TBX1 p.Pro57Ser (c.169C>T) in the general population?

TBX1 p.Pro57Ser (c.169C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TBX1 p.Pro57Ser (c.169C>T)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

TBX1 p.Pro57Ser

c.169C>T · VCV4731595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DiGeorge syndrome

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -9.51	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 6.3	GERP -1.4, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 412 bp · p 0.048 · regional, not allelic
Overall
CADD	17.58	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P48S vs ClinVar P57S) — verify the residue.

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: TBX1
Protein: p.Pro57Ser
Coding: c.169C>T
MANE Select: NM_001379200
Type: single nucleotide variant
Location: chr22:19761012 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.12 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 70.15 · 1 PDB
Residue 57: the 'disordered' region

Full TBX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DiGeorge syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TBX1 p.Pro57Leu Uncertain significance ★ ⚠ same residue
TBX1 p.Pro57_Arg58insProPro Uncertain significance ★ same residue
TBX1 p.Pro57_Pro76del Conflicting classifications of pathogenicity ★ same residue
TBX1 p.Pro57dup Conflicting classifications of pathogenicity ★ same residue
TBX1 p.Pro57Arg Uncertain significance ★ ⚠ same residue
TBX1 p.Pro57= Likely benign ★ same residue
TBX1 c.711+1G>A Pathogenic/Likely pathogenic ★★ same condition
TBX1 p.Ala21Thr Likely pathogenic ★★ 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/tbx1-p-pro57ser (accessed [today's date]).

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