CBS c.736+281A>C
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 6.96%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +281 | deep intronic (+281 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.076 | GERP -1.4 |
| Overall | ||
| CADD | 1.922 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.96%
African / African-American · 85/1,222 alleles
Filtering AF
5.76%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.32%
Overall
1.59%
94/5,910 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.96% | 14 |
| Middle Eastern | 3.57% | 28 |
| Admixed American | 0.914% | 109 |
| Remaining individualsnot grpmax-eligible | 0.893% | 112 |
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
- Coding
- c.736+281A>C
- MANE Select
- NM_000071
- dbSNP
- rs115877954
- Type
- single nucleotide variant
- Location
- chr21:43064922 (GRCh38)
- Structure
- AlphaFold pLDDT 90.15 · 28 PDB
Similar variants
- CBS c.1145+1G>A Pathogenic/Likely pathogenic ★★ same type
- CBS c.1223+1G>T Pathogenic ★★ same type
- CBS c.1224-2A>C Pathogenic ★★ same type
- CBS c.1358+1G>A Pathogenic ★★ same type
- CBS c.1359-1G>C Pathogenic/Likely pathogenic ★★ same type
- CBS c.1468-1G>A Likely pathogenic ★★ same type
- CBS c.1552+1G>A Pathogenic/Likely pathogenic ★★ same type
- CBS c.209+1G>A Pathogenic/Likely pathogenic ★★ same type
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-c-736-plus-281a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown