Is CBS p.Ala288= (c.864A>C) pathogenic?

CBS p.Ala288= (c.864A>C) is classified Likely benign in CBS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-28). Absent from gnomAD v4.1; Associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED.

What condition is associated with CBS p.Ala288= (c.864A>C)?

CBS p.Ala288= (c.864A>C) is associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is CBS p.Ala288= (c.864A>C) in the general population?

CBS p.Ala288= (c.864A>C) is absent from gnomAD v4.1 (gnomAD).

CBS p.Ala288=

c.864A>C · rs2146367182 · VCV1575282

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	acceptor loss · deltas
Constraint at this position
Conservation	phyloP -10	GERP -2.1
Overall
CADD	0.724	PHRED · no single calibrated threshold — expert panels disagree

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.Ala288=
Coding: c.864A>C
MANE Select: NM_000071
dbSNP: rs2146367182
Type: single nucleotide variant
Location: chr21:43063043 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 288: a β-strand; a UniProt-annotated variant site (in cbsd); a UniProt-annotated variant site (in cbsd; protein expression is comparable to wild-type; significant decrease of enzyme activity)

Full CBS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial thoracic aortic aneurysm and aortic dissection

Similar variants

CBS p.Ala288Thr Pathogenic/Likely pathogenic ★★ ⚠ same residue
CBS p.Ala288Ser Uncertain significance ★★ ⚠ same residue
CBS p.Ala288Pro Likely pathogenic ★ same residue
CBS c.1145+1G>A Pathogenic/Likely pathogenic ★★ same condition
CBS c.1223+1G>T Pathogenic ★★ same condition
CBS c.1224-2A>C Pathogenic ★★ same condition
CBS c.1552+1G>A Pathogenic/Likely pathogenic ★★ same condition
CBS c.451+1G>T 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-ala288 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown