Is CBS p.Lys406del (c.1213AAG[1]) pathogenic?

CBS p.Lys406del (c.1213AAG[1]) is classified Uncertain significance in CBS (ClinVar, Single submitter, 2 submitters; last evaluated 2016-02-18). Absent from gnomAD; Associated with classic homocystinuria.

What condition is associated with CBS p.Lys406del (c.1213AAG[1])?

CBS p.Lys406del (c.1213AAG[1]) is associated with classic homocystinuria (ClinVar).

How common is CBS p.Lys406del (c.1213AAG[1]) in the general population?

CBS p.Lys406del (c.1213AAG[1]) is absent from gnomAD (gnomAD).

CBS p.Lys406del

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.

c.1213AAG[1] · rs780555741 · VCV420533

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

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 11	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
Protein: p.Lys406del
Coding: c.1213AAG[1]
MANE Select: NM_000071
dbSNP: rs780555741
Type: Microsatellite
Location: chr21:43059231 (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

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 p.Lys406fs Pathogenic/Likely pathogenic ★★ same residue
CBS p.Cys244_Asp245delinsTer Pathogenic/Likely pathogenic ★★ same condition
CBS p.Ser500fs Pathogenic ★★ same condition
CBS p.Lys406Gln Uncertain significance ★ ⚠ same residue
CBS c.1145+1G>A Pathogenic/Likely pathogenic ★★ same condition
CBS c.1223+1G>T Pathogenic ★★ same condition
CBS c.1224-2A>C Pathogenic ★★ same condition
CBS c.1358+1G>A 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-lys406del (accessed [today's date]).

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