Is CBS p.Ser500= (c.1500G>C) pathogenic?

CBS p.Ser500= (c.1500G>C) is classified Likely benign in CBS (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-12). Very rare (popmax 0.00914%, eas); Associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED.

What condition is associated with CBS p.Ser500= (c.1500G>C)?

CBS p.Ser500= (c.1500G>C) is associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED (ClinVar).

How common is CBS p.Ser500= (c.1500G>C) in the general population?

CBS p.Ser500= (c.1500G>C) is very rare (popmax 0.00914%, eas) (gnomAD).

CBS p.Ser500=

c.1500G>C · rs1057522901 · VCV1135892

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00914%, eas)

Conditions

HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.027	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.5	GERP -1.2
Overall
CADD	0.198	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00914% East Asian · 1/10,942 alleles

Overall 0.000608% 1/164,420 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.Ser500=
Coding: c.1500G>C
MANE Select: NM_000071
dbSNP: rs1057522901
Type: single nucleotide variant
Location: chr21:43056855 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 500: a UniProt-annotated variant site (in cbsd; no effect on cystathionine beta-synthase activity; altered stimulation by adomet); 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

Similar variants

CBS p.Ser500Leu Uncertain significance ★★ ⚠ same residue
CBS p.Ser500fs Pathogenic ★★ same residue
CBS c.1145+1G>A Pathogenic/Likely pathogenic ★★ same condition
CBS c.1223+1G>T 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-ser500 (accessed [today's date]).

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