Is CBS p.Pro200= (c.600G>A) pathogenic?

CBS p.Pro200= (c.600G>A) is classified Conflicting classifications of pathogenicity in CBS (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-25). Very rare (popmax 0.00193%, sas); Associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED.

What condition is associated with CBS p.Pro200= (c.600G>A)?

CBS p.Pro200= (c.600G>A) is associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED, classic homocystinuria, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is CBS p.Pro200= (c.600G>A) in the general population?

CBS p.Pro200= (c.600G>A) is very rare (popmax 0.00193%, sas) (gnomAD).

CBS p.Pro200=

c.600G>A · rs181472622 · VCV340087

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00193%, sas)

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 -15	GERP -2.5
Overall
CADD	1.437	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00193% South Asian · 1/51,760 alleles

Overall 0.000448% 2/446,834 alleles · very rare exomes 2/427,724 · genomes 0/19,110 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00193%	51,760
European (non-Finnish)	0.00041%	243,962

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.Pro200=
Coding: c.600G>A
MANE Select: NM_000071
dbSNP: rs181472622
Type: single nucleotide variant
Location: chr21:43065453 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 200: a β-strand; a UniProt-annotated variant site (in cbsd)

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: classic homocystinuria familial thoracic aortic aneurysm and aortic dissection

Similar variants

CBS p.Pro200Leu Uncertain significance ★★ ⚠ same residue
CBS p.Pro200Arg 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.1358+1G>A Pathogenic ★★ same condition
CBS c.1359-1G>C Pathogenic/Likely pathogenic ★★ same condition
CBS c.1468-1G>A 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-pro200 (accessed [today's date]).

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