Is CBS p.Asn212= (c.636C>T) pathogenic?

CBS p.Asn212= (c.636C>T) is classified Benign in CBS (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-02). Low-frequency (popmax 2.13%, eas); Associated with connective tissue disorder.

What condition is associated with CBS p.Asn212= (c.636C>T)?

CBS p.Asn212= (c.636C>T) is associated with connective tissue disorder, classic homocystinuria, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is CBS p.Asn212= (c.636C>T) in the general population?

CBS p.Asn212= (c.636C>T) is low-frequency (popmax 2.13%, eas) (gnomAD).

CBS p.Asn212=

c.636C>T · rs2298758 · VCV136668

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.13%, eas)

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 -5.4	GERP -2.5
Overall
CADD	0.761	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.13% East Asian · 690/32,374 alleles

Filtering AF 2% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.95%

Overall 0.185% 865/468,662 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.13%	47
Remaining individualsnot grpmax-eligible	0.117%	857
South Asian	0.0852%	1,174
Middle Eastern	0.0509%	1,966
European (non-Finnish)	0.0372%	2,690
Finnishnot grpmax-eligible	0.00665%	15,031

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.Asn212=
Coding: c.636C>T
MANE Select: NM_000071
dbSNP: rs2298758
Type: single nucleotide variant
Location: chr21:43065417 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 212: an α-helix

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.Asn212Lys Uncertain significance ★ ⚠ 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
CBS c.1552+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-asn212 (accessed [today's date]).

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