Is CC2D2A p.Val682fs (c.2043dup) pathogenic?

CC2D2A p.Val682fs (c.2043dup) is classified Pathogenic in CC2D2A (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-23). Very rare (popmax 8.53e-05%, nfe); Associated with Joubert syndrome.

What condition is associated with CC2D2A p.Val682fs (c.2043dup)?

CC2D2A p.Val682fs (c.2043dup) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is CC2D2A p.Val682fs (c.2043dup) in the general population?

CC2D2A p.Val682fs (c.2043dup) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

CC2D2A p.Val682fs

c.2043dup · rs1718392791 · VCV2939411

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

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 17 of 37
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP 0.27, phastCons 0.99

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.53e-05% European (non-Finnish) · 1/1,172,818 alleles

Overall 6.91e-05% 1/1,447,120 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: CC2D2A
Protein: p.Val682fs
Coding: c.2043dup
MANE Select: NM_001378615
dbSNP: rs1718392791
Type: Duplication
Location: chr4:15540875 (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.Val682= Likely benign ★ same residue
CC2D2A p.Ala1362fs Pathogenic/Likely pathogenic ★★ same condition
CC2D2A p.Glu1259Ter Pathogenic ★★ same condition
CC2D2A p.Phe744fs Pathogenic/Likely pathogenic ★★ same condition
CC2D2A p.Pro1250fs Pathogenic/Likely pathogenic ★★ same condition
CC2D2A p.Val1583fs Uncertain significance ★★ same condition
CC2D2A c.1150-15dup Likely benign ★★ same condition
CC2D2A c.2922+10dup Benign/Likely benign ★★ 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-val682fs (accessed [today's date]).

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