CBS p.Arg336Cys
c.1005_1006delinsTT · rs1064793703 · VCV419185
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Not reported
no gnomAD frequency available for this variant
Conditions
1
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 9.5 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 0.00 | constrained · MANE · 11 kb · p 6.7e-07 · regional, not allelic |
| 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.Arg336Cys
- Coding
- c.1005_1006delinsTT
- MANE Select
- NM_000071
- dbSNP
- rs1064793703
- Type
- Indel
- Location
- chr21:43062344 (GRCh38)
- Structure
- AlphaFold pLDDT 90.15 · 28 PDB
- Residue 336
- an α-helix; a UniProt-annotated variant site (in cbsd; protein expression is comparable to wild-type; loss of activity; absent capacity to form multimeric quaternary structure); a UniProt-annotated variant site (in cbsd; mild form; no effect on expression; exhibits an activity lower than 4% of the wild-type enzyme; altered stimulation by adomet; absent capacity to form multimeric quaternary structure)
Similar variants
- CBS p.Arg336Pro Pathogenic/Likely pathogenic ★★ same residue
- CBS p.Arg336Ser Likely pathogenic ★ same residue
- CBS p.Arg336Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- CBS p.Arg336= Likely benign ★ same residue
- CBS p.Arg336His Pathogenic/Likely pathogenic ★★ ⚠ same residue
- CBS p.Thr135_Leu136= Likely benign ★ same condition
- CBS p.Arg336_Met337insTer Likely pathogenic same residue
- CBS c.1145+1G>A 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-arg336cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown