CREB3L3 p.Pro58=
c.174C>T · VCV4752564
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0083%, 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 -9.4 | GERP -3.9 |
| Overall | ||
| CADD | 0.085 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0083%
European (non-Finnish) · 98/1,180,016 alleles
Filtering AF
0.00697%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.00682%
110/1,614,070 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0083% | 12,041 |
| South Asian | 0.00549% | 18,216 |
| Admixed American | 0.00333% | 29,987 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| African / African-American | 0.00267% | 37,510 |
| Finnishnot grpmax-eligible | 0.00156% | 64,020 |
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
- CREB3L3
- Protein
- p.Pro58=
- Coding
- c.174C>T
- MANE Select
- NM_032607
- Type
- single nucleotide variant
- Location
- chr19:4157012 (GRCh38)
- Gene constraint
- LOEUF 1.155 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.26
- Residue 58
- a UniProt-annotated variant site (in hytg2; risk factor; loss of transactivation activity in apoa4, apoc2 or fgf21 promoter-driven luciferase assays); the 'disordered' region
Similar variants
- CREB3L3 p.Arg175Ter Pathogenic/Likely pathogenic ★★ same type
- CREB3L3 p.Arg204Ter Pathogenic/Likely pathogenic ★★ same type
- CREB3L3 p.Arg242Ter Pathogenic/Likely pathogenic ★★ same type
- CREB3L3 p.Trp46Ter Pathogenic/Likely pathogenic ★★ same type
- CREB3L3 c.457+5G>A Uncertain significance ★★ same type
- CREB3L3 p.Ala111Thr Uncertain significance ★★ ⚠ same type
- CREB3L3 p.Ala167Thr Uncertain significance ★★ ⚠ same type
- CREB3L3 p.Ala442Val 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/creb3l3-p-pro58 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown