C2CD3 p.Gln280=
c.840G>A · rs139995248 · VCV714412
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.594%, mid)
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 1.1 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 7.176 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.594%
Middle Eastern · 36/6,062 alleles
Filtering AF
0.441%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.388%
Overall
0.00774%
125/1,614,052 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.594% | 168 |
| Admixed American | 0.0433% | 2,308 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,906 |
| South Asian | 0.00549% | 18,216 |
| European (non-Finnish) | 0.00356% | 28,094 |
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
- C2CD3
- Protein
- p.Gln280=
- Coding
- c.840G>A
- MANE Select
- NM_001286577
- dbSNP
- rs139995248
- Type
- single nucleotide variant
- Location
- chr11:74138835 (GRCh38)
- Gene constraint
- LOEUF 0.637 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.65
Similar variants
- C2CD3 c.3911-2A>T Pathogenic/Likely pathogenic ★★ same type
- C2CD3 p.Arg621Ter Pathogenic/Likely pathogenic ★★ same type
- C2CD3 p.Arg666Ter Pathogenic ★★ same type
- C2CD3 p.Arg768Ter Pathogenic/Likely pathogenic ★★ same type
- C2CD3 p.Tyr173Ter Pathogenic/Likely pathogenic ★★ same type
- C2CD3 c.2085+5G>A Uncertain significance ★★ same type
- C2CD3 c.4951+6C>T Uncertain significance ★★ same type
- C2CD3 c.5495+4A>G 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/c2cd3-p-gln280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown