Is CBS p.Thr191= (c.573G>A) pathogenic?

CBS p.Thr191= (c.573G>A) is classified Benign/Likely benign in CBS (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-06-01). Low-frequency (popmax 4.09%, mid); Associated with connective tissue disorder.

What condition is associated with CBS p.Thr191= (c.573G>A)?

CBS p.Thr191= (c.573G>A) is associated with connective tissue disorder, classic homocystinuria, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is CBS p.Thr191= (c.573G>A) in the general population?

CBS p.Thr191= (c.573G>A) is low-frequency (popmax 4.09%, mid) (gnomAD).

CBS p.Thr191=

c.573G>A · rs73906420 · VCV136667

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.09%, mid)

Conditions

connective tissue disorder

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 -20	GERP -2.5
Overall
CADD	0.564	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.09% Middle Eastern · 76/1,860 alleles

Filtering AF 3.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.08%

Overall 0.871% 3,774/433,412 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	4.09%	24
Ashkenazi Jewishnot grpmax-eligible	3.95%	25
South Asian	1.09%	92
Remaining individualsnot grpmax-eligible	0.992%	101
European (non-Finnish)	0.898%	111
African / African-American	0.698%	143
Admixed American	0.412%	243
Finnishnot grpmax-eligible	0.0395%	2,533

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.Thr191=
Coding: c.573G>A
MANE Select: NM_000071
dbSNP: rs73906420
Type: single nucleotide variant
Location: chr21:43065480 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 191: a β-strand; a UniProt-annotated variant site (in cbsd; moderate and severe forms; loss of cystathionine beta-synthase activity; absent capacity to form multimeric quaternary structure)

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

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: classic homocystinuria familial thoracic aortic aneurysm and aortic dissection

Similar variants

CBS p.Thr191Met Pathogenic ★★ same residue
CBS p.Thr191Lys Conflicting classifications of pathogenicity ★ ⚠ 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.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

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-thr191 (accessed [today's date]).

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