Is CBS p.Ser27fs (c.78dup) pathogenic?

CBS p.Ser27fs (c.78dup) is classified Pathogenic in CBS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-03). Absent from gnomAD; Associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED.

What condition is associated with CBS p.Ser27fs (c.78dup)?

CBS p.Ser27fs (c.78dup) is associated with HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED (ClinVar).

How common is CBS p.Ser27fs (c.78dup) in the general population?

CBS p.Ser27fs (c.78dup) is absent from gnomAD (gnomAD).

CBS p.Ser27fs

c.78dup · rs2517483668 · VCV2033813

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.17	GERP -2.6
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.Ser27fs
Coding: c.78dup
MANE Select: NM_000071
dbSNP: rs2517483668
Type: Duplication
Location: chr21:43072115 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 27: the 'disordered' region; a modified residue (phosphoserine)

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.Ser27dup Uncertain significance ★★ same residue
CBS p.Ala71fs Pathogenic ★★ same condition
CBS p.Met126fs Pathogenic ★★ same condition
CBS p.Asp281fs Pathogenic ★ same condition
CBS p.Gln298fs Pathogenic ★ same condition
CBS p.Glu62fs Pathogenic ★ same condition
CBS p.Ile143fs Pathogenic ★ same condition
CBS p.Thr87fs 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-ser27fs (accessed [today's date]).

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