Is CBS c.738del pathogenic?

CBS c.738del is classified Pathogenic in CBS (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-11-10). Absent from gnomAD; Associated with classic homocystinuria.

What condition is associated with CBS c.738del?

CBS c.738del is associated with classic homocystinuria, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is CBS c.738del in the general population?

CBS c.738del is absent from gnomAD (gnomAD).

CBS c.738del

Q: How is Homocystinuria due to cystathionine beta-synthase deficiency inherited?

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

rs766453711 · VCV370105

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

classic homocystinuria

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 4.1	GERP 1.1, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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
Coding: c.738del
MANE Select: NM_000071
dbSNP: rs766453711
Type: Deletion
Location: chr21:43063990 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB

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

Disease context

classic homocystinuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial thoracic aortic aneurysm and aortic dissection

For Homocystinuria due to cystathionine beta-synthase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

CBS c.209+1_209+8del Likely pathogenic ★★ same condition
CBS c.209+1del Pathogenic ★★ same condition
CBS c.667-14_667-7del Pathogenic/Likely pathogenic ★★ same condition
CBS p.Arg161fs Pathogenic/Likely pathogenic ★★ same condition
CBS p.Arg51fs Pathogenic/Likely pathogenic ★★ same condition
CBS p.Asn194fs Pathogenic/Likely pathogenic ★★ same condition
CBS p.Leu230fs Pathogenic ★★ same condition
CBS p.Lys247_Gly256del 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-c-738del (accessed [today's date]).

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