Is CBS p.Ala360= (c.1080C>T) pathogenic?

CBS p.Ala360= (c.1080C>T) is classified Benign in CBS (ClinVar, Multiple submitters, 19 submitters; last evaluated 2026-02-04). Common (popmax 60.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with classic homocystinuria.

What condition is associated with CBS p.Ala360= (c.1080C>T)?

CBS p.Ala360= (c.1080C>T) is associated with classic homocystinuria, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

CBS p.Ala360=

Q: How common is CBS p.Ala360= (c.1080C>T) in the general population?

CBS p.Ala360= (c.1080C>T) is common (popmax 60.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Homocystinuria due to cystathionine beta-synthase deficiency inherited?

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

c.1080C>T · rs1801181 · VCV92424

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 19 submitters

gnomAD v4.1

Common

common (popmax 60.9%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

classic homocystinuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.009	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -2.2
Overall
CADD	0.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 60.9% East Asian · 1,772/2,908 alleles

Filtering AF 58.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 57.6%

Overall 38.1% 15,727/41,226 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	60.9%	2
Finnishnot grpmax-eligible	52.4%	2
European (non-Finnish)	42.3%	2
Remaining individualsnot grpmax-eligible	41.9%	2
Ashkenazi Jewishnot grpmax-eligible	38.1%	3
Middle Eastern	35.6%	3
South Asian	34.1%	3
Admixed American	21.2%	5
African / African-American	5.71%	18

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.Ala360=
Coding: c.1080C>T
MANE Select: NM_000071
dbSNP: rs1801181
Type: single nucleotide variant
Location: chr21:43060506 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 360: an α-helix

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

Disease context

classic homocystinuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial thoracic aortic aneurysm and aortic dissection

For Homocystinuria due to cystathionine beta-synthase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

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
CBS c.1552+1G>A Pathogenic/Likely pathogenic ★★ same condition
CBS c.209+1G>A 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-ala360 (accessed [today's date]).

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