Is CC2D2A p.Pro610= (c.1830G>A) pathogenic?

CC2D2A p.Pro610= (c.1830G>A) is classified Conflicting classifications of pathogenicity in CC2D2A (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-28). Rare (popmax 0.248%, eas); Associated with Meckel syndrome, type 6.

What condition is associated with CC2D2A p.Pro610= (c.1830G>A)?

CC2D2A p.Pro610= (c.1830G>A) is associated with Meckel syndrome, type 6, Joubert syndrome 9, Joubert syndrome (ClinVar).

How common is CC2D2A p.Pro610= (c.1830G>A) in the general population?

CC2D2A p.Pro610= (c.1830G>A) is rare (popmax 0.248%, eas) (gnomAD).

CC2D2A p.Pro610=

c.1830G>A · rs185072004 · VCV498727

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.248%, eas)

Conditions

Meckel syndrome, type 6

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 -4.4	GERP -4.8
Overall
CADD	1.658	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.248% East Asian · 111/44,716 alleles

Filtering AF 0.211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.197%

Overall 0.014% 225/1,609,974 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.248%	403
Remaining individualsnot grpmax-eligible	0.0802%	1,247
South Asian	0.0156%	6,426
African / African-American	0.0147%	6,815
Ashkenazi Jewishnot grpmax-eligible	0.0102%	9,838
European (non-Finnish)	0.00297%	33,663
Admixed American	0.00168%	59,526

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.Pro610=
Coding: c.1830G>A
MANE Select: NM_001378615
dbSNP: rs185072004
Type: single nucleotide variant
Location: chr4:15537964 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 610: 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

Similar variants

CC2D2A p.Pro610Leu 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-pro610 (accessed [today's date]).

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