CREB3L3 p.Pro399=
c.1197C>T · rs140601919 · VCV1565592
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.112%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.122 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.5 | GERP -2.5 |
| Overall | ||
| CADD | 4.167 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.112%
African / African-American · 84/75,016 alleles
Filtering AF
0.0926%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0855%
Overall
0.00868%
140/1,613,472 alleles · rare
exomes 86/1,461,218 · genomes 54/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.112% | 893 |
| East Asian | 0.0156% | 6,410 |
| South Asian | 0.00769% | 13,012 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,835 |
| European (non-Finnish) | 0.00322% | 31,053 |
| Admixed American | 0.00167% | 60,022 |
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.Pro399=
- Coding
- c.1197C>T
- MANE Select
- NM_032607
- dbSNP
- rs140601919
- Type
- single nucleotide variant
- Location
- chr19:4171780 (GRCh38)
- Gene constraint
- LOEUF 1.155 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.26
- Residue 399
- 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-pro399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown