CBS p.Gly348Ser
c.1042G>A · VCV3257396
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3538 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3538 | ambiguous |
|---|---|---|
| REVEL | 0.92 | moderately pathogenic-leaning |
| SaProt | LLR -12.99 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | acceptor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP 7.4 | GERP 1.1, phastCons 1 |
| Regional constraint | o/e 0.00 | constrained · MANE · 11 kb · p 6.7e-07 · regional, not allelic |
| Overall | ||
| CADD | 32.0 | 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.Gly348Ser
- Coding
- c.1042G>A
- MANE Select
- NM_000071
- Type
- single nucleotide variant
- Location
- chr21:43060544 (GRCh38)
- Structure
- AlphaFold pLDDT 90.15 · 28 PDB
- Residue 348
- an α-helix
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-p-gly348ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown