Is CC2D2A p.Ser1067= (c.3201G>A) pathogenic?

CC2D2A p.Ser1067= (c.3201G>A) is classified Benign in CC2D2A (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). Common (popmax 25.5%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Joubert syndrome.

What condition is associated with CC2D2A p.Ser1067= (c.3201G>A)?

CC2D2A p.Ser1067= (c.3201G>A) is associated with Joubert syndrome, Meckel syndrome, type 6, Joubert syndrome 9 (ClinVar).

CC2D2A p.Ser1067=

Q: How common is CC2D2A p.Ser1067= (c.3201G>A) in the general population?

CC2D2A p.Ser1067= (c.3201G>A) is common (popmax 25.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3201G>A · rs73125627 · VCV126237

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Common

common (popmax 25.5%, nfe) — too common for a highly-penetrant pathogenic allele

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 -8.9	GERP -4.6
Overall
CADD	0.116	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 25.5% European (non-Finnish) · 300,292/1,178,178 alleles

Filtering AF 25.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 25.4%

Overall 23.7% 382,533/1,611,182 alleles · common exomes 351,680/1,459,204 · genomes 30,853/151,978 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	28.1%	4
European (non-Finnish)grpmax	25.5%	4
Ashkenazi Jewishnot grpmax-eligible	22.9%	4
Remaining individualsnot grpmax-eligible	22.6%	4
South Asian	20.5%	5
Middle Eastern	20.1%	5
Admixed American	17.8%	6
Amishnot grpmax-eligible	13.3%	8
African / African-American	12.8%	8
East Asian	7.36%	14

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser1067=
Coding: c.3201G>A
MANE Select: NM_001378615
dbSNP: rs73125627
Type: single nucleotide variant
Location: chr4:15567395 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 1067: the c2 domain; the 'disordered' region

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.Ser1067Leu Uncertain significance ★★ ⚠ same residue
CC2D2A p.Ser1067Pro 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

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-ser1067 (accessed [today's date]).

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