Is CC2D2A p.Ile825= (c.2475C>T) pathogenic?

CC2D2A p.Ile825= (c.2475C>T) is classified Benign/Likely benign in CC2D2A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Rare (popmax 0.797%, afr); Associated with Joubert syndrome.

What condition is associated with CC2D2A p.Ile825= (c.2475C>T)?

CC2D2A p.Ile825= (c.2475C>T) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is CC2D2A p.Ile825= (c.2475C>T) in the general population?

CC2D2A p.Ile825= (c.2475C>T) is rare (popmax 0.797%, afr) (gnomAD).

CC2D2A p.Ile825=

c.2475C>T · rs113835820 · VCV166803

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.797%, afr)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.2	GERP -5.2
Overall
CADD	2.633	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.797% African / African-American · 597/74,918 alleles

Filtering AF 0.744% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.723%

Overall 0.048% 774/1,612,204 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.797%	125
Remaining individualsnot grpmax-eligible	0.0721%	1,387
Admixed American	0.0452%	2,212
European (non-Finnish)	0.00856%	11,676
South Asian	0.00442%	22,645

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.Ile825=
Coding: c.2475C>T
MANE Select: NM_001378615
dbSNP: rs113835820
Type: single nucleotide variant
Location: chr4:15553294 (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 c.1017+1G>A Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.123+2T>G Likely pathogenic ★★ same condition
CC2D2A c.1359+1G>C Likely pathogenic ★★ same condition
CC2D2A c.1466+1G>A Likely pathogenic ★★ same condition
CC2D2A c.1466+2T>C Likely pathogenic ★★ same condition
CC2D2A c.1608-2A>G Likely pathogenic ★★ same condition
CC2D2A c.2004-17A>G Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.2486+1G>A 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-ile825 (accessed [today's date]).

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