Is CBS p.Gln243= (c.729G>A) pathogenic?

CBS p.Gln243= (c.729G>A) is classified Likely benign in CBS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-05). Very rare (popmax 0.0002%, nfe); Associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED.

What condition is associated with CBS p.Gln243= (c.729G>A)?

CBS p.Gln243= (c.729G>A) is associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is CBS p.Gln243= (c.729G>A) in the general population?

CBS p.Gln243= (c.729G>A) is very rare (popmax 0.0002%, nfe) (gnomAD).

CBS p.Gln243=

c.729G>A · rs749466749 · VCV2121156

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0002%, nfe)

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 0.92	GERP 1.2, phastCons 1
Overall
CADD	7.696	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0002% European (non-Finnish) · 2/999,218 alleles

Filtering AF 3.3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000158% 2/1,268,842 alleles · very rare

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.Gln243=
Coding: c.729G>A
MANE Select: NM_000071
dbSNP: rs749466749
Type: single nucleotide variant
Location: chr21:43065210 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 243: an α-helix

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: familial thoracic aortic aneurysm and aortic dissection

Similar variants

CBS p.Gln243Ter Pathogenic ★★ 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.1552+1G>A Pathogenic/Likely pathogenic ★★ same condition
CBS c.451+1G>T Likely pathogenic ★★ same condition
CBS c.531+1G>A Likely pathogenic ★★ same condition
CBS c.736+2T>G 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-gln243 (accessed [today's date]).

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