C2CD2 p.Pro104=
c.312G>A · rs58190987 · VCV777623
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.26%, afr)
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 -11 | GERP -5 |
| Overall | ||
| CADD | 0.333 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.26%
African / African-American · 1,652/73,084 alleles
Filtering AF
2.17%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.13%
Overall
0.117%
1,812/1,549,588 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.26% | 44 |
| Admixed American | 0.137% | 728 |
| Remaining individualsnot grpmax-eligible | 0.113% | 881 |
| East Asian | 0.0171% | 5,847 |
| South Asian | 0.00595% | 16,796 |
| European (non-Finnish) | 0.000872% | 114,681 |
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
- C2CD2
- Protein
- p.Pro104=
- Coding
- c.312G>A
- MANE Select
- NM_015500
- dbSNP
- rs58190987
- Type
- single nucleotide variant
- Location
- chr21:41942213 (GRCh38)
- Gene constraint
- LOEUF 0.924 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.52
- Residue 104
- the smp-lbd domain
Similar variants
- C2CD2 p.Ala123Val Uncertain significance ★ ⚠ same type
- C2CD2 p.Ala136Gly Uncertain significance ★ ⚠ same type
- C2CD2 p.Ala146Val Uncertain significance ★ ⚠ same type
- C2CD2 p.Ala189Thr Uncertain significance ★ ⚠ same type
- C2CD2 p.Ala207Val Uncertain significance ★ ⚠ same type
- C2CD2 p.Ala345Val Uncertain significance ★ ⚠ same type
- C2CD2 p.Ala466Thr Uncertain significance ★ ⚠ same type
- C2CD2 p.Ala492Val Uncertain significance ★ ⚠ same type
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/c2cd2-p-pro104 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown