Is CC2D2A p.Pro1603Arg (c.4808C>G) pathogenic?

CC2D2A p.Pro1603Arg (c.4808C>G) is classified Uncertain significance in CC2D2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-08). AlphaMissense: likely pathogenic (0.5915); Absent from gnomAD v4.1; Associated with Joubert syndrome.

What condition is associated with CC2D2A p.Pro1603Arg (c.4808C>G)?

CC2D2A p.Pro1603Arg (c.4808C>G) is associated with Joubert syndrome, Meckel syndrome (ClinVar).

How common is CC2D2A p.Pro1603Arg (c.4808C>G) in the general population?

CC2D2A p.Pro1603Arg (c.4808C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CC2D2A p.Pro1603Arg (c.4808C>G)?

AlphaMissense predicts likely pathogenic (score 0.5915) — an in-silico prediction, not a clinical call.

CC2D2A p.Pro1603Arg

c.4808C>G · rs2148497490 · VCV1358193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5915 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Joubert syndrome

Computational evidence

Protein change
AlphaMissense	0.5915	likely pathogenic
REVEL	0.764	pathogenic-leaning
SaProt	LLR -9.44	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 14 kb · p 0.69 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CC2D2A
Protein: p.Pro1603Arg
Coding: c.4808C>G
MANE Select: NM_001378615
dbSNP: rs2148497490
Type: single nucleotide variant
Location: chr4:15601370 (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.Pro1603= Conflicting classifications of pathogenicity ★ 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
CC2D2A c.2004-17A>G 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-pro1603arg (accessed [today's date]).

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