Is CBS p.Arg132= (c.396C>T) pathogenic?

CBS p.Arg132= (c.396C>T) is classified Likely benign in CBS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Very rare (popmax 0.00189%, amr); Associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED.

What condition is associated with CBS p.Arg132= (c.396C>T)?

CBS p.Arg132= (c.396C>T) is associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is CBS p.Arg132= (c.396C>T) in the general population?

CBS p.Arg132= (c.396C>T) is very rare (popmax 0.00189%, amr) (gnomAD).

CBS p.Arg132=

c.396C>T · rs754758476 · VCV1571850

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00189%, amr)

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 -4.9	GERP -2.6
Overall
CADD	1.756	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00189% Admixed American · 1/52,968 alleles

Filtering AF 0.000468% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000338%

Overall 0.00104% 10/957,640 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00189%	52,968
South Asian	0.00134%	74,402
European (non-Finnish)	0.00109%	91,948

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.Arg132=
Coding: c.396C>T
MANE Select: NM_000071
dbSNP: rs754758476
Type: single nucleotide variant
Location: chr21:43066298 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 132: an α-helix

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.Arg132Ser Uncertain significance ★★ ⚠ same residue
CBS p.Arg132Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CBS p.Arg132His 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

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-arg132 (accessed [today's date]).

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