CCN4 p.Asp148=
c.444C>T · rs755626224 · VCV740749
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, 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 -8 | GERP -1.5 |
| Overall | ||
| CADD | 5.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00206%
Overall
0.000991%
16/1,613,958 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Admixed American | 0.00833% | 12,003 |
| East Asian | 0.00223% | 44,888 |
| South Asian | 0.0022% | 45,547 |
| African / African-American | 0.00133% | 74,952 |
| European (non-Finnish) | 0.000508% | 196,667 |
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.Asp148=
- Coding
- c.444C>T
- MANE Select
- NM_003882
- dbSNP
- rs755626224
- Type
- single nucleotide variant
- Location
- chr8:133220675 (GRCh38)
- Gene constraint
- LOEUF 1.151 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.16
- Residue 148
- the vwfc domain
Similar variants
- CCN4 p.Arg97= Benign ★★ same type
- CCN4 p.Leu99= 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
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-asp148 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown