Is CBS p.Ser117= (c.351C>T) pathogenic?

CBS p.Ser117= (c.351C>T) is classified Likely benign in CBS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-24). Very rare (popmax 0.00254%, eas); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with CBS p.Ser117= (c.351C>T)?

CBS p.Ser117= (c.351C>T) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is CBS p.Ser117= (c.351C>T) in the general population?

CBS p.Ser117= (c.351C>T) is very rare (popmax 0.00254%, eas) (gnomAD).

CBS p.Ser117=

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.351C>T · rs769149281 · VCV519585

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00254%, eas)

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 -3	GERP -2.6
Overall
CADD	9.162	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00254% East Asian · 1/39,316 alleles

Filtering AF 0.00052% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000334%

Overall 0.00104% 8/772,702 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00254%	39,316
European (non-Finnish)	0.00125%	79,907

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.Ser117=
Coding: c.351C>T
MANE Select: NM_000071
dbSNP: rs769149281
Type: single nucleotide variant
Location: chr21:43066343 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 117: a β-strand

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.Ser117Cys 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
CBS p.Arg121His Pathogenic/Likely pathogenic ★★ same condition
CBS p.Arg125Gln 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-ser117 (accessed [today's date]).

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