Is CBS p.Ile516fs (c.1545del) pathogenic?

CBS p.Ile516fs (c.1545del) is classified Likely pathogenic in CBS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-09-08). Absent from gnomAD; Associated with classic homocystinuria.

What condition is associated with CBS p.Ile516fs (c.1545del)?

CBS p.Ile516fs (c.1545del) is associated with classic homocystinuria (ClinVar).

How common is CBS p.Ile516fs (c.1545del) in the general population?

CBS p.Ile516fs (c.1545del) is absent from gnomAD (gnomAD).

CBS p.Ile516fs

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.1545del · rs1555871095 · VCV553823

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

classic homocystinuria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (16 of 17, 7 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.9	GERP 1.1, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ile516fs
Coding: c.1545del
MANE Select: NM_000071
dbSNP: rs1555871095
Type: Deletion
Location: chr21:43056810 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB

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.209+1_209+8del Likely pathogenic ★★ same condition
CBS c.209+1del Pathogenic ★★ same condition
CBS c.667-14_667-7del Pathogenic/Likely pathogenic ★★ same condition
CBS c.738del Pathogenic ★★ same condition
CBS p.Arg161fs Pathogenic/Likely pathogenic ★★ same condition
CBS p.Arg51fs Pathogenic/Likely pathogenic ★★ same condition
CBS p.Asn194fs Pathogenic/Likely pathogenic ★★ same condition
CBS p.Leu230fs 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-ile516fs (accessed [today's date]).

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