Is CC2D2A p.Val64= (c.192G>A) pathogenic?

CC2D2A p.Val64= (c.192G>A) is classified Conflicting classifications of pathogenicity in CC2D2A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0133%, amr); Associated with Meckel syndrome.

What condition is associated with CC2D2A p.Val64= (c.192G>A)?

CC2D2A p.Val64= (c.192G>A) is associated with Meckel syndrome, Joubert syndrome (ClinVar).

How common is CC2D2A p.Val64= (c.192G>A) in the general population?

CC2D2A p.Val64= (c.192G>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

CC2D2A p.Val64=

c.192G>A · rs745986665 · VCV290389

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Conditions

Meckel syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.134	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.61	GERP -2.7
Overall
CADD	1.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/59,970 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.000616% 9/1,461,154 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,496
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Val64=
Coding: c.192G>A
MANE Select: NM_001378615
dbSNP: rs745986665
Type: single nucleotide variant
Location: chr4:15480772 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 69.46
Residue 64: the 'disordered' region

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

Disease context

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

Also linked: Joubert syndrome

Similar variants

CC2D2A c.1017+1G>A Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.123+2T>G 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
CC2D2A c.2004-17A>G Pathogenic/Likely pathogenic ★★ same condition
CC2D2A c.2486+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-val64 (accessed [today's date]).

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