CREB3L3 p.Pro445=
c.1335G>A · rs749480478 · VCV2187816
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
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 -2.1 |
| Overall | ||
| CADD | 0.057 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,820 alleles
Filtering AF
0.000555%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000931%
15/1,611,500 alleles · very rare
exomes 15/1,459,172 · genomes 0/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,910 |
| East Asian | 0.00223% | 44,834 |
| African / African-American | 0.00133% | 75,020 |
| European (non-Finnish) | 0.000933% | 107,213 |
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.Pro445=
- Coding
- c.1335G>A
- MANE Select
- NM_032607
- dbSNP
- rs749480478
- Type
- single nucleotide variant
- Location
- chr19:4171918 (GRCh38)
- Gene constraint
- LOEUF 1.155 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.26
- Residue 445
- the 'disordered' region; a UniProt-annotated variant site (in hytg2; risk factor; loss of transactivation activity in apoa4, apoc2 or fgf21 promoter-driven luciferase assays)
Similar variants
- CREB3L3 p.Pro445Gln Uncertain significance ★ ⚠ same residue
- CREB3L3 p.Pro445Leu Uncertain significance ★ ⚠ same residue
- CREB3L3 p.Pro445Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro445 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown