CREB3 p.Val175=
c.525T>C · rs146674074 · VCV2659183
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.683%, afr)
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 0.48 | GERP -3.5, phastCons 0.99 |
| Overall | ||
| CADD | 6.392 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.683%
African / African-American · 509/74,558 alleles
Filtering AF
0.634%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.614%
Overall
0.0359%
578/1,609,984 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.683% | 146 |
| Middle Eastern | 0.0993% | 1,007 |
| Remaining individualsnot grpmax-eligible | 0.0449% | 2,226 |
| Admixed American | 0.0409% | 2,445 |
| South Asian | 0.00111% | 90,202 |
| European (non-Finnish) | 0.000848% | 117,896 |
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
- CREB3
- Protein
- p.Val175=
- Coding
- c.525T>C
- MANE Select
- NM_001255978 · reported on NM_006368
- dbSNP
- rs146674074
- Type
- single nucleotide variant
- Location
- chr9:35735198 (GRCh38)
- Structure
- AlphaFold pLDDT 61.56
Similar variants
- CREB3 c.697-5T>C Benign ★★ same type
- CREB3 p.Asn222= Benign ★★ same type
- CREB3 p.Ala113Val Uncertain significance ★ ⚠ same type
- CREB3 p.Arg153Cys Uncertain significance ★ ⚠ same type
- CREB3 p.Arg155Pro Uncertain significance ★ ⚠ same type
- CREB3 p.Arg155Trp Uncertain significance ★ ⚠ same type
- CREB3 p.Arg168Cys Uncertain significance ★ ⚠ same type
- CREB3 p.Arg264Cys 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/creb3-p-val175 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown