Is CBS p.Asn149fs (c.444dup) pathogenic?

CBS p.Asn149fs (c.444dup) is classified Pathogenic in CBS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-14). Very rare (popmax 0.000806%, nfe); Associated with CBS-related disorder.

What condition is associated with CBS p.Asn149fs (c.444dup)?

CBS p.Asn149fs (c.444dup) is associated with CBS-related disorder (ClinVar).

How common is CBS p.Asn149fs (c.444dup) in the general population?

CBS p.Asn149fs (c.444dup) is very rare (popmax 0.000806%, nfe) (gnomAD).

CBS p.Asn149fs

c.444dup · rs2146393621 · VCV1456891

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000806%, nfe)

Conditions

CBS-related disorder

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 5 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, 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

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000806% European (non-Finnish) · 8/993,154 alleles

Filtering AF 0.000347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00025%

Overall 0.00065% 8/1,230,994 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.Asn149fs
Coding: c.444dup
MANE Select: NM_000071
dbSNP: rs2146393621
Type: Duplication
Location: chr21:43066249 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 28 PDB
Residue 149: an α-helix; a binding site

Full CBS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CBS-related disorder

Similar variants

CBS p.Asn149= Likely benign ★★ same residue
CBS c.209+1G>A Pathogenic/Likely pathogenic ★★ same condition
CBS p.Ala114Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
CBS p.Ala158Val Pathogenic/Likely pathogenic ★★ same condition
CBS p.Ala331Glu Pathogenic/Likely pathogenic ★★ same condition
CBS p.Ala355Pro Likely pathogenic ★★ same condition
CBS p.Arg121Cys Pathogenic/Likely pathogenic ★★ same condition
CBS p.Arg125Gln 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-asn149fs (accessed [today's date]).

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