CREB3L1 p.Pro421=
c.1263C>T · VCV4691942
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0683%, sas)
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 |
| Overall | ||
| CADD | 7.358 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0683%
South Asian · 61/89,338 alleles
Filtering AF
0.0545%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0495%
Overall
0.00431%
69/1,600,624 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0683% | 1,465 |
| Middle Eastern | 0.0335% | 2,984 |
| Remaining individualsnot grpmax-eligible | 0.00485% | 20,611 |
| East Asian | 0.00223% | 44,758 |
| European (non-Finnish) | 0.00017% | 586,638 |
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.Pro421=
- Coding
- c.1263C>T
- MANE Select
- NM_052854
- Type
- single nucleotide variant
- Location
- chr11:46320268 (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-pro421 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown