CBS p.Asp444His
c.1330G>C · VCV4803217
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.6791 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
Computational evidence
| Protein change | ||
| AlphaMissense | 0.6791 | likely pathogenic ✓ concordant with ClinVar |
|---|---|---|
| REVEL | 0.876 | moderately pathogenic-leaning |
| SaProt | LLR -16.61 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.6 | GERP 1.2, phastCons 1 |
| Regional constraint | o/e 0.00 | constrained · MANE · 11 kb · p 6.7e-07 · regional, not allelic |
| Overall | ||
| CADD | 26.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CBS
- Protein
- p.Asp444His
- Coding
- c.1330G>C
- MANE Select
- NM_000071
- Type
- single nucleotide variant
- Location
- chr21:43058862 (GRCh38)
- Structure
- AlphaFold pLDDT 90.15 · 28 PDB
- Residue 444
- the cbs domain; a UniProt-annotated variant site (in cbsd; decreased expression; no effect on cystathionine beta-synthase activity; altered stimulation by adomet; increased homotetramer formation); a β-strand
Similar variants
- CBS p.Asp444Asn Pathogenic/Likely pathogenic ★★ ⚠ same residue
- CBS p.Asp444= Likely benign ★★ same residue
- CBS c.1145+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CBS c.1223+1G>T Pathogenic ★★ same condition
- CBS c.1552+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CBS c.451+1G>T Likely pathogenic ★★ same condition
- CBS c.531+1G>A Likely pathogenic ★★ same condition
- CBS c.736+2T>G 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-asp444his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown