CC2D2A p.Pro721=
c.2163G>A · rs768337150 · VCV194817
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0288%, afr)
Conditions
2
Meckel 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 -12 | GERP -4.6 |
| Overall | ||
| CADD | 0.197 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0288%
African / African-American · 21/72,942 alleles
Filtering AF
0.0192%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0161%
Overall
0.00219%
34/1,549,268 alleles · ultra-rare
exomes 18/1,397,184 · genomes 16/152,084 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0288% | 3,473 |
| Middle Eastern | 0.0167% | 6,006 |
| Admixed American | 0.00394% | 25,408 |
| East Asian | 0.00244% | 40,908 |
| South Asian | 0.00239% | 41,865 |
| Finnishnot grpmax-eligible | 0.00167% | 59,848 |
| European (non-Finnish) | 0.000524% | 190,934 |
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.Pro721=
- Coding
- c.2163G>A
- MANE Select
- NM_001378615
- dbSNP
- rs768337150
- Type
- single nucleotide variant
- Location
- chr4:15540996 (GRCh38)
- Gene constraint
- LOEUF 0.854 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 69.46
- Residue 721
- a UniProt-annotated variant site (in jbts9)
Similar variants
- CC2D2A p.Pro721Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- CC2D2A p.Pro721Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-pro721 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown