Is CC2D2A p.Val533fs (c.1596del) pathogenic?

CC2D2A p.Val533fs (c.1596del) is classified Pathogenic in CC2D2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-18). Absent from gnomAD; Associated with Joubert syndrome.

What condition is associated with CC2D2A p.Val533fs (c.1596del)?

CC2D2A p.Val533fs (c.1596del) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is CC2D2A p.Val533fs (c.1596del) in the general population?

CC2D2A p.Val533fs (c.1596del) is absent from gnomAD (gnomAD).

CC2D2A p.Val533fs

c.1596del · rs2474966060 · VCV2943505

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

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 14 of 37
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1

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: CC2D2A
Protein: p.Val533fs
Coding: c.1596del
MANE Select: NM_001378615
dbSNP: rs2474966060
Type: Deletion
Location: chr4:15533321 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46

Full CC2D2A 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

Also linked: Meckel syndrome

Similar variants

CC2D2A p.Val533Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
CC2D2A c.3289delG Pathogenic ★★ same condition
CC2D2A c.3597_3600del Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.4179+1del Pathogenic ★★ same condition
CC2D2A p.Ala1197fs Pathogenic/Likely pathogenic ★★ same condition
CC2D2A p.Ala447fs Pathogenic/Likely pathogenic ★★ same condition
CC2D2A p.Asp1489fs Pathogenic/Likely pathogenic ★★ same condition
CC2D2A p.Gln280fs 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/cc2d2a-p-val533fs (accessed [today's date]).

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