Is CBS p.Glu400del (c.1194GGA[2]) pathogenic?

CBS p.Glu400del (c.1194GGA[2]) is classified Uncertain significance in CBS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-19). Absent from gnomAD v4.1; Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with CBS p.Glu400del (c.1194GGA[2])?

CBS p.Glu400del (c.1194GGA[2]) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is CBS p.Glu400del (c.1194GGA[2]) in the general population?

CBS p.Glu400del (c.1194GGA[2]) is absent from gnomAD v4.1 (gnomAD).

CBS p.Glu400del

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1194GGA[2] · rs745438246 · VCV340082

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 120)

Conditions

familial thoracic aortic aneurysm and aortic dissection

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.05	GERP -2.3
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 120). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CBS
Protein: p.Glu400del
Coding: c.1194GGA[2]
MANE Select: NM_000071
dbSNP: rs745438246
Type: Microsatellite
Location: chr21:43059247 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 400: an α-helix

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

Disease context

familial thoracic aortic aneurysm and aortic dissection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

CBS p.Glu400= Likely benign ★ same residue
CBS c.1224-2A>C Pathogenic ★★ same condition
CBS c.667-14_667-7del Pathogenic/Likely pathogenic ★★ same condition
CBS c.738del Pathogenic ★★ same condition
CBS c.954+1G>A Pathogenic/Likely pathogenic ★★ same condition
CBS p.Ala114Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
CBS p.Ala288Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
CBS p.Ala331Glu Pathogenic/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/cbs-p-glu400del (accessed [today's date]).

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