Is CBS p.Ile84= (c.252C>T) pathogenic?

CBS p.Ile84= (c.252C>T) is classified Likely benign in CBS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-02). Very rare (popmax 0.000444%, nfe); Associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED.

What condition is associated with CBS p.Ile84= (c.252C>T)?

CBS p.Ile84= (c.252C>T) is associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is CBS p.Ile84= (c.252C>T) in the general population?

CBS p.Ile84= (c.252C>T) is very rare (popmax 0.000444%, nfe) (gnomAD).

CBS p.Ile84=

c.252C>T · rs1180701001 · VCV1112476

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000444%, nfe)

Conditions

HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -2.8
Overall
CADD	4.874	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000444% European (non-Finnish) · 1/225,092 alleles

Overall 0.000274% 1/364,782 alleles · very rare

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.Ile84=
Coding: c.252C>T
MANE Select: NM_000071
dbSNP: rs1180701001
Type: single nucleotide variant
Location: chr21:43068573 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 84: a β-strand

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.Ile84Thr Uncertain significance ★ ⚠ 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
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-ile84 (accessed [today's date]).

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