Is CBY1 p.Asn23fs (c.64_65dup) pathogenic?

CBY1 p.Asn23fs (c.6465dup) is classified Pathogenic in CBY1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-01-01). Very rare (popmax 0.0011%, sas); Associated with Joubert syndrome.

What condition is associated with CBY1 p.Asn23fs (c.64_65dup)?

CBY1 p.Asn23fs (c.64_65dup) is associated with Joubert syndrome (ClinVar).

How common is CBY1 p.Asn23fs (c.64_65dup) in the general population?

CBY1 p.Asn23fs (c.64_65dup) is very rare (popmax 0.0011%, sas) (gnomAD).

CBY1 p.Asn23fs

c.64_65dup · rs1318058212 · VCV694265

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Joubert syndrome

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 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.1	GERP -5

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,010 alleles

Overall 0.000137% 2/1,459,260 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,010
European (non-Finnish)	8.49e-05%	1,177,622

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: CBY1
Protein: p.Asn23fs
Coding: c.64_65dup
MANE Select: NM_015373
dbSNP: rs1318058212
Type: Microsatellite
Location: chr22:38668111 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 86.54 · 1 PDB
Residue 23: the 'disordered' region

Full CBY1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CBY1 p.Gly64_Val65insTer 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/cby1-p-asn23fs (accessed [today's date]).

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