Is CBS p.Glu404del (c.1210_1212del) pathogenic?

CBS p.Glu404del (c.12101212del) is classified Uncertain significance in CBS (ClinVar, Single submitter, 2 submitters; last evaluated 2021-08-31). Absent from gnomAD; Associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED.

What condition is associated with CBS p.Glu404del (c.1210_1212del)?

CBS p.Glu404del (c.1210_1212del) is associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED, classic homocystinuria (ClinVar).

How common is CBS p.Glu404del (c.1210_1212del) in the general population?

CBS p.Glu404del (c.1210_1212del) is absent from gnomAD (gnomAD).

CBS p.Glu404del

c.1210_1212del · rs1555872822 · VCV557273

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

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 1.1	GERP -2.3, phastCons 0.92
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
Protein: p.Glu404del
Coding: c.1210_1212del
MANE Select: NM_000071
dbSNP: rs1555872822
Type: Deletion
Location: chr21:43059237 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 404: an α-helix

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

Disease context

HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: classic homocystinuria

Similar variants

CBS p.Glu404Ter Likely pathogenic ★ same residue
CBS p.Glu404Asp Uncertain significance ★ ⚠ same residue
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 c.738del Pathogenic ★★ same condition
CBS p.Arg161fs Pathogenic/Likely pathogenic ★★ same condition
CBS p.Arg51fs 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-glu404del (accessed [today's date]).

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