Is CC2D2A p.Pro1603= (c.4809C>G) pathogenic?

CC2D2A p.Pro1603= (c.4809C>G) is classified Conflicting classifications of pathogenicity in CC2D2A (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-02-02). Ultra-rare (popmax 0.0497%, nfe); Associated with Meckel syndrome.

What condition is associated with CC2D2A p.Pro1603= (c.4809C>G)?

CC2D2A p.Pro1603= (c.4809C>G) is associated with Meckel syndrome, optic atrophy, Meckel syndrome, type 6 (ClinVar).

How common is CC2D2A p.Pro1603= (c.4809C>G) in the general population?

CC2D2A p.Pro1603= (c.4809C>G) is ultra-rare (popmax 0.0497%, nfe) (gnomAD).

CC2D2A p.Pro1603=

c.4809C>G · rs367841700 · VCV282741

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0497%, nfe)

Conditions

Meckel 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 1.4	GERP -1.3, phastCons 1
Overall
CADD	7.638	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0497% European (non-Finnish) · 578/1,162,352 alleles

Filtering AF 0.0464% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.045%

Overall 0.0379% 600/1,583,370 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0497%	2,011
Remaining individualsnot grpmax-eligible	0.0212%	4,715
African / African-American	0.00944%	10,588
Admixed American	0.00354%	28,288

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.Pro1603=
Coding: c.4809C>G
MANE Select: NM_001378615
dbSNP: rs367841700
Type: single nucleotide variant
Location: chr4:15601371 (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

Meckel syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: optic atrophy Meckel syndrome, type 6 Joubert syndrome 9 Joubert syndrome

Similar variants

CC2D2A p.Pro1603Arg Uncertain significance ★ ⚠ same residue
CC2D2A c.1017+1G>A Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.1149+1G>A Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.123+2T>G Likely pathogenic ★★ same condition
CC2D2A c.1359+1G>A Pathogenic/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

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-pro1603 (accessed [today's date]).

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