CREB3L3 p.Phe342=
c.1026T>C · rs531193592 · VCV2721558
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.103%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.099 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.43 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -2 | GERP -3.2 |
| Overall | ||
| CADD | 6.589 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.103%
South Asian · 94/91,080 alleles
Filtering AF
0.0863%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.08%
Overall
0.019%
306/1,614,124 alleles · rare
exomes 295/1,461,884 · genomes 11/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.103% | 969 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,209 |
| European (non-Finnish) | 0.0169% | 5,930 |
| Admixed American | 0.00167% | 60,006 |
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.Phe342=
- Coding
- c.1026T>C
- MANE Select
- NM_032607
- dbSNP
- rs531193592
- Type
- single nucleotide variant
- Location
- chr19:4171433 (GRCh38)
- Gene constraint
- LOEUF 1.155 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.26
- Residue 342
- 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.Phe342Leu 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
- CREB3L3 p.Ala111Thr Uncertain significance ★★ ⚠ same type
- CREB3L3 p.Ala167Thr 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-phe342 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown