Is CC2D2A p.Ser52= (c.156C>T) pathogenic?

CC2D2A p.Ser52= (c.156C>T) is classified Benign in CC2D2A (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 23.8%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Joubert syndrome 1.

What condition is associated with CC2D2A p.Ser52= (c.156C>T)?

CC2D2A p.Ser52= (c.156C>T) is associated with Joubert syndrome 1, Meckel syndrome, type 6, Joubert syndrome 9 (ClinVar).

CC2D2A p.Ser52=

Q: How common is CC2D2A p.Ser52= (c.156C>T) in the general population?

CC2D2A p.Ser52= (c.156C>T) is common (popmax 23.8%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.156C>T · rs1861050 · VCV126229

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 23.8%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

Joubert syndrome 1

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 -13	GERP -4.5
Overall
CADD	0.157	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 23.8% Admixed American · 14,113/59,354 alleles

Filtering AF 23.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.3%

Overall 5.32% 85,694/1,610,996 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	23.8%	4
East Asian	16.4%	6
African / African-American	11%	9
South Asian	6.79%	15
Finnishnot grpmax-eligible	5.74%	17
Amishnot grpmax-eligible	5.59%	18
Remaining individualsnot grpmax-eligible	5.52%	18
European (non-Finnish)	3.58%	28
Middle Eastern	3.52%	28
Ashkenazi Jewishnot grpmax-eligible	0.958%	104

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.Ser52=
Coding: c.156C>T
MANE Select: NM_001378615
dbSNP: rs1861050
Type: single nucleotide variant
Location: chr4:15480736 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 52: the 'disordered' region

Full CC2D2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

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
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-ser52 (accessed [today's date]).

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