Is CC2D2A p.Pro201= (c.603C>T) pathogenic?

CC2D2A p.Pro201= (c.603C>T) is classified Conflicting classifications of pathogenicity in CC2D2A (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.042%, sas); Associated with Meckel syndrome, type 6.

What condition is associated with CC2D2A p.Pro201= (c.603C>T)?

CC2D2A p.Pro201= (c.603C>T) is associated with Meckel syndrome, type 6, Joubert syndrome 9, Joubert syndrome (ClinVar).

How common is CC2D2A p.Pro201= (c.603C>T) in the general population?

CC2D2A p.Pro201= (c.603C>T) is ultra-rare (popmax 0.042%, sas) (gnomAD).

CC2D2A p.Pro201=

c.603C>T · rs556542553 · VCV199055

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 0.042%, sas)

Conditions

Meckel syndrome, type 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.88 · evaluated, not missing
Constraint at this position
Conservation	phyloP -10	GERP -5.2
Overall
CADD	0.503	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.042% South Asian · 37/88,014 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0276%

Overall 0.00475% 76/1,600,430 alleles · ultra-rare exomes 58/1,448,248 · genomes 18/152,182 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.042%	2,379
African / African-American	0.0323%	3,093
Remaining individualsnot grpmax-eligible	0.00323%	30,984
East Asian	0.00226%	44,156
Admixed American	0.00174%	57,444
European (non-Finnish)	0.000936%	106,784

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.Pro201=
Coding: c.603C>T
MANE Select: NM_001378615
dbSNP: rs556542553
Type: single nucleotide variant
Location: chr4:15511309 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 201: the 'disordered' region

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

Disease context

Meckel syndrome, type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome 9 Joubert syndrome Meckel syndrome retinitis pigmentosa 93 COACH syndrome 2

Similar variants

CC2D2A p.Pro201Arg 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-pro201 (accessed [today's date]).

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