Is CC2D2A p.Arg948= (c.2844G>A) pathogenic?

CC2D2A p.Arg948= (c.2844G>A) is classified Conflicting classifications of pathogenicity in CC2D2A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-09). Ultra-rare (popmax 0.058%, nfe); Associated with Joubert syndrome.

What condition is associated with CC2D2A p.Arg948= (c.2844G>A)?

CC2D2A p.Arg948= (c.2844G>A) is associated with Joubert syndrome, Meckel syndrome, type 6, Joubert syndrome 9 (ClinVar).

How common is CC2D2A p.Arg948= (c.2844G>A) in the general population?

CC2D2A p.Arg948= (c.2844G>A) is ultra-rare (popmax 0.058%, nfe) (gnomAD).

CC2D2A p.Arg948=

c.2844G>A · rs182369056 · VCV347844

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.058%, nfe)

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 0.014	GERP -4.6, phastCons 0.032
Overall
CADD	5.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.058% European (non-Finnish) · 664/1,145,702 alleles

Filtering AF 0.0543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0528%

Overall 0.0452% 700/1,548,428 alleles · ultra-rare exomes 656/1,396,162 · genomes 44/152,266 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.058%	1,725
Remaining individualsnot grpmax-eligible	0.0465%	2,149
African / African-American	0.011%	9,126

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.Arg948=
Coding: c.2844G>A
MANE Select: NM_001378615
dbSNP: rs182369056
Type: single nucleotide variant
Location: chr4:15559179 (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, type 6 Joubert syndrome 9 Meckel syndrome

Similar variants

CC2D2A p.Arg948Trp Uncertain significance ★★ ⚠ same residue
CC2D2A p.Arg948Gln Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg948 (accessed [today's date]).

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