Is CBS p.Gln298= (c.894G>A) pathogenic?

CBS p.Gln298= (c.894G>A) is classified Conflicting classifications of pathogenicity in CBS (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-26). Absent from gnomAD v4.1; Associated with classic homocystinuria.

What condition is associated with CBS p.Gln298= (c.894G>A)?

CBS p.Gln298= (c.894G>A) is associated with classic homocystinuria, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is CBS p.Gln298= (c.894G>A) in the general population?

CBS p.Gln298= (c.894G>A) is absent from gnomAD v4.1 (gnomAD).

CBS p.Gln298=

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.894G>A · rs370514077 · VCV236939

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

classic homocystinuria

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 2.5	GERP 0.019, phastCons 0.99
Overall
CADD	5.971	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CBS
Protein: p.Gln298=
Coding: c.894G>A
MANE Select: NM_000071
dbSNP: rs370514077
Type: single nucleotide variant
Location: chr21:43063013 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB

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-gln298 (accessed [today's date]).

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