Is TBX1 p.Phe3= (c.9C>T) pathogenic?

TBX1 p.Phe3= (c.9C>T) is classified Likely benign in TBX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-14). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with TBX1 p.Phe3= (c.9C>T)?

TBX1 p.Phe3= (c.9C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is TBX1 p.Phe3= (c.9C>T) in the general population?

TBX1 p.Phe3= (c.9C>T) is absent from gnomAD v4.1 (gnomAD).

TBX1 p.Phe3=

c.9C>T · VCV3804878

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

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 4.7	GERP 1.2, phastCons 1
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

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.Phe3=
Coding: c.9C>T
MANE Select: NM_001379200 · reported on NM_080647
Type: single nucleotide variant
Location: chr22:19759652 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.12 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 70.15 · 1 PDB

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TBX1 p.Ala104Val Uncertain significance ★★ ⚠ same condition
TBX1 p.Ala108Glu Uncertain significance ★★ ⚠ same condition
TBX1 p.Ala114Glu Uncertain significance ★★ ⚠ same condition
TBX1 p.Ala197Val Uncertain significance ★★ ⚠ same condition
TBX1 p.Ala213Thr Uncertain significance ★★ ⚠ same condition
TBX1 p.Ala24Thr Uncertain significance ★★ ⚠ same condition
TBX1 p.Ala32Val Uncertain significance ★★ ⚠ same condition
TBX1 p.Ala347Thr 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/tbx1-p-phe3 (accessed [today's date]).

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