CBS p.Leu499=
c.1497C>G · rs1477206467 · VCV1077735
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00609%, sas)
Conditions
1
HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.651 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.29 | GERP -1.9, phastCons 0.97 |
| Overall | ||
| CADD | 1.545 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00609%
South Asian · 2/32,866 alleles
Filtering AF
0.00101%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000377%
Overall
0.00119%
2/167,718 alleles · very rare
exomes 2/165,584 · genomes 0/2,134 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- CBS
- Protein
- p.Leu499=
- Coding
- c.1497C>G
- MANE Select
- NM_000071
- dbSNP
- rs1477206467
- Type
- single nucleotide variant
- Location
- chr21:43056858 (GRCh38)
- Structure
- AlphaFold pLDDT 90.15 · 28 PDB
- Residue 499
- an α-helix
Similar variants
- 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
- CBS c.954+1G>A Pathogenic/Likely pathogenic ★★ same condition
- CBS p.Ala226Thr 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-leu499 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown