CREB3L1 p.Ser399=
c.1197C>T · rs60813863 · VCV1221887
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 12.6%, afr) — too common for a highly-penetrant pathogenic allele
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 -1.3 | GERP -2.6 |
| Overall | ||
| CADD | 11.67 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
12.6%
African / African-American · 9,455/74,982 alleles
Filtering AF
12.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 12.3%
Overall
0.679%
10,961/1,613,632 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 12.6% | 8 |
| Amishnot grpmax-eligible | 1.64% | 61 |
| Remaining individualsnot grpmax-eligible | 0.957% | 104 |
| Admixed American | 0.926% | 108 |
| Middle Eastern | 0.594% | 168 |
| Ashkenazi Jewishnot grpmax-eligible | 0.125% | 800 |
| South Asian | 0.0351% | 2,846 |
| European (non-Finnish) | 0.0196% | 5,108 |
| East Asian | 0.00223% | 44,856 |
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
- CREB3L1
- Protein
- p.Ser399=
- Coding
- c.1197C>T
- MANE Select
- NM_052854
- dbSNP
- rs60813863
- Type
- single nucleotide variant
- Location
- chr11:46317426 (GRCh38)
- Gene constraint
- LOEUF 0.954 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.66
Similar variants
- CREB3L1 p.Ala151Ser Uncertain significance ★★ ⚠ same type
- CREB3L1 p.Ala369Thr Uncertain significance ★★ ⚠ same type
- CREB3L1 p.Ala95Val Uncertain significance ★★ ⚠ same type
- CREB3L1 p.Arg223Cys Uncertain significance ★★ ⚠ same type
- CREB3L1 p.Arg236His Uncertain significance ★★ ⚠ same type
- CREB3L1 p.Arg268Trp Uncertain significance ★★ ⚠ same type
- CREB3L1 p.Arg308Cys Uncertain significance ★★ ⚠ same type
- CREB3L1 p.Arg462Trp 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/creb3l1-p-ser399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown