CCN4 p.Leu99=
c.297C>T · rs114585111 · VCV783535
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.09%, 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 0.6 | GERP -3.8, phastCons 1 |
| Overall | ||
| CADD | 9.743 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.09%
African / African-American · 821/75,052 alleles
Filtering AF
1.03%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.01%
Overall
0.0618%
997/1,614,040 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.09% | 91 |
| Admixed American | 0.167% | 600 |
| Remaining individualsnot grpmax-eligible | 0.102% | 977 |
| Middle Eastern | 0.0495% | 2,019 |
| South Asian | 0.00439% | 22,772 |
| European (non-Finnish) | 0.000424% | 235,977 |
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
- CCN4
- Protein
- p.Leu99=
- Coding
- c.297C>T
- MANE Select
- NM_003882
- dbSNP
- rs114585111
- Type
- single nucleotide variant
- Location
- chr8:133213091 (GRCh38)
- Gene constraint
- LOEUF 1.151 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.16
- Residue 99
- a disulfide bond; the igfbp n-terminal domain
Similar variants
- CCN4 p.Arg97= Benign ★★ same type
- CCN4 p.Thr145Met Likely benign ★★ ⚠ same type
- CCN4 p.Ala10Glu Uncertain significance ★ same type
- CCN4 p.Ala10Thr Uncertain significance ★ ⚠ same type
- CCN4 p.Ala17Ser Uncertain significance ★ ⚠ same type
- CCN4 p.Ala196Thr Uncertain significance ★ ⚠ same type
- CCN4 p.Ala243Ser Uncertain significance ★ ⚠ same type
- CCN4 p.Ala288Val 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/ccn4-p-leu99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown