Is CBS p.Arg498= (c.1494G>A) pathogenic?

CBS p.Arg498= (c.1494G>A) is classified Likely benign in CBS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-16). Absent from gnomAD v4.1; Associated with classic homocystinuria.

What condition is associated with CBS p.Arg498= (c.1494G>A)?

CBS p.Arg498= (c.1494G>A) is associated with classic homocystinuria (ClinVar).

How common is CBS p.Arg498= (c.1494G>A) in the general population?

CBS p.Arg498= (c.1494G>A) is absent from gnomAD v4.1 (gnomAD).

CBS p.Arg498=

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.1494G>A · rs778800147 · VCV510461

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 167,064)

Conditions

classic homocystinuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.04	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.78	GERP -1.9
Overall
CADD	2.791	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 167,064). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CBS
Protein: p.Arg498=
Coding: c.1494G>A
MANE Select: NM_000071
dbSNP: rs778800147
Type: single nucleotide variant
Location: chr21:43056861 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 498: an α-helix

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

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-arg498 (accessed [today's date]).

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