Is CC2D2A p.Ala323= (c.969A>G) pathogenic?

CC2D2A p.Ala323= (c.969A>G) is classified Likely benign in CC2D2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-21). Very rare (popmax 0.00464%, eas); Associated with Joubert syndrome.

What condition is associated with CC2D2A p.Ala323= (c.969A>G)?

CC2D2A p.Ala323= (c.969A>G) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is CC2D2A p.Ala323= (c.969A>G) in the general population?

CC2D2A p.Ala323= (c.969A>G) is very rare (popmax 0.00464%, eas) (gnomAD).

CC2D2A p.Ala323=

c.969A>G · rs763921042 · VCV1077272

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00464%, eas)

Conditions

Joubert syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -5.5
Overall
CADD	0.063	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00464% East Asian · 2/43,106 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000498%

Overall 0.000316% 5/1,580,282 alleles · very rare exomes 3/1,428,090 · genomes 2/152,192 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00464%	21,553
African / African-American	0.00404%	24,733

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.Ala323=
Coding: c.969A>G
MANE Select: NM_001378615
dbSNP: rs763921042
Type: single nucleotide variant
Location: chr4:15515956 (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.Ala323Thr Uncertain significance ★★ ⚠ same residue
CC2D2A p.Ala323Val Uncertain significance ★ ⚠ same residue
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

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-ala323 (accessed [today's date]).

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