Is CC2D2A p.Val732= (c.2196C>T) pathogenic?

CC2D2A p.Val732= (c.2196C>T) is classified Conflicting classifications of pathogenicity in CC2D2A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-05). Ultra-rare (popmax 0.0114%, eas); Associated with Joubert syndrome.

What condition is associated with CC2D2A p.Val732= (c.2196C>T)?

CC2D2A p.Val732= (c.2196C>T) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is CC2D2A p.Val732= (c.2196C>T) in the general population?

CC2D2A p.Val732= (c.2196C>T) is ultra-rare (popmax 0.0114%, eas) (gnomAD).

CC2D2A p.Val732=

c.2196C>T · rs764246302 · VCV596515

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0114%, eas)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.6	GERP -4.9
Overall
CADD	1.728	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0114% East Asian · 5/44,022 alleles

Filtering AF 0.00442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0029%

Overall 0.00102% 16/1,570,754 alleles · ultra-rare exomes 15/1,418,430 · genomes 1/152,324 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0114%	8,804
African / African-American	0.00134%	74,440
European (non-Finnish)	0.000871%	114,756

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.Val732=
Coding: c.2196C>T
MANE Select: NM_001378615
dbSNP: rs764246302
Type: single nucleotide variant
Location: chr4:15550838 (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-val732 (accessed [today's date]).

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