Is CBS p.Arg209= (c.625C>A) pathogenic?

CBS p.Arg209= (c.625C>A) is classified Likely benign in CBS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-20). Rare (popmax 0.131%, sas); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with CBS p.Arg209= (c.625C>A)?

CBS p.Arg209= (c.625C>A) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is CBS p.Arg209= (c.625C>A) in the general population?

CBS p.Arg209= (c.625C>A) is rare (popmax 0.131%, sas) (gnomAD).

CBS p.Arg209=

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.625C>A · rs137939628 · VCV413349

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.131%, sas)

Conditions

familial thoracic aortic aneurysm and aortic dissection

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 1.2	GERP -1.4, phastCons 1
Overall
CADD	9.087	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.131% South Asian · 72/54,880 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0979%

Overall 0.03% 138/459,710 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.131%	762
Finnishnot grpmax-eligible	0.0444%	2,252
European (non-Finnish)	0.0192%	5,207
Remaining individualsnot grpmax-eligible	0.00813%	12,303
Admixed American	0.00608%	16,437
African / African-American	0.0054%	18,508

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.Arg209=
Coding: c.625C>A
MANE Select: NM_000071
dbSNP: rs137939628
Type: single nucleotide variant
Location: chr21:43065428 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 209: an α-helix

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

Disease context

familial thoracic aortic aneurysm and aortic dissection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

CBS p.Arg209Trp Uncertain significance ★ ⚠ same residue
CBS p.Arg209Gln Uncertain significance ★★ ⚠ same residue
CBS p.Arg209Pro Uncertain significance ★ ⚠ same residue
CBS c.1224-2A>C Pathogenic ★★ same condition
CBS c.954+1G>A Pathogenic/Likely pathogenic ★★ same condition
CBS p.Ala114Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
CBS p.Ala288Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
CBS p.Ala331Glu Pathogenic/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-arg209 (accessed [today's date]).

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