CAVIN4 p.Pro228=
c.684G>A · rs148428476 · VCV1195515
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0785%, nfe)
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 -20 | GERP -4.2 |
| Overall | ||
| CADD | 0.179 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0785%
European (non-Finnish) · 926/1,180,022 alleles
Filtering AF
0.0742%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0725%
Overall
0.06%
969/1,614,160 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0785% | 1,274 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,976 |
| Admixed American | 0.0167% | 6,002 |
| African / African-American | 0.012% | 8,338 |
| East Asian | 0.00668% | 14,962 |
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
- CAVIN4
- Protein
- p.Pro228=
- Coding
- c.684G>A
- MANE Select
- NM_001018116
- dbSNP
- rs148428476
- Type
- single nucleotide variant
- Location
- chr9:100586040 (GRCh38)
- Gene constraint
- LOEUF 0.875 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 66.21
Similar variants
- CAVIN4 p.Pro228Ala Uncertain significance ★ ⚠ same residue
- CAVIN4 p.Pro228Leu Uncertain significance ★ ⚠ same residue
- CAVIN4 p.Arg17Cys Uncertain significance ★★ ⚠ same type
- CAVIN4 p.Arg272Cys Uncertain significance ★★ ⚠ same type
- CAVIN4 p.Asn128Lys Uncertain significance ★★ ⚠ same type
- CAVIN4 p.Pro142Leu Uncertain significance ★★ ⚠ same type
- CAVIN4 p.Ser20Thr Uncertain significance ★★ ⚠ same type
- CAVIN4 c.408+28T>C Likely benign ★★ 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/cavin4-p-pro228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown