C2CD3 p.Leu919=
c.2755C>T · rs17132707 · VCV1226980
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 8.43%, amr) — too common for a highly-penetrant pathogenic allele
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 1.9, phastCons 1 |
| Overall | ||
| CADD | 11.93 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.43%
Admixed American · 5,062/60,018 alleles
Filtering AF
8.24%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.16%
Overall
5.39%
87,001/1,613,812 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 8.43% | 12 |
| East Asian | 7.12% | 14 |
| Finnishnot grpmax-eligible | 6.69% | 15 |
| European (non-Finnish) | 5.9% | 17 |
| Remaining individualsnot grpmax-eligible | 4.26% | 23 |
| Ashkenazi Jewishnot grpmax-eligible | 1.89% | 53 |
| Amishnot grpmax-eligible | 1.21% | 83 |
| African / African-American | 1.02% | 98 |
| South Asian | 0.895% | 112 |
| Middle Eastern | 0.61% | 164 |
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.Leu919=
- Coding
- c.2755C>T
- MANE Select
- NM_001286577
- dbSNP
- rs17132707
- Type
- single nucleotide variant
- Location
- chr11:74098233 (GRCh38)
- Gene constraint
- LOEUF 0.637 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.65
- Residue 919
- the c2 2 domain
Similar variants
- C2CD3 p.Leu919Val Uncertain significance ★ ⚠ same residue
- 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
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-leu919 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown