CREBBP p.Arg75Ter
c.223C>T · rs2141496166 · VCV1701038
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
CREBBP-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 31 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.1 | GERP -0.25, phastCons 1 |
| Overall | ||
| CADD | 37.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CREBBP
- Protein
- p.Arg75Ter
- Coding
- c.223C>T
- MANE Select
- NM_004380
- dbSNP
- rs2141496166
- Type
- single nucleotide variant
- Location
- chr16:3850872 (GRCh38)
- Gene constraint
- LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 54.31 · 144 PDB
- Residue 75
- the 'disordered' region
Disease context
CREBBP-related disorder
Similar variants
- CREBBP p.Arg75Gln Uncertain significance ★★ ⚠ same residue
- CREBBP p.Arg75= Likely benign ★ same residue
- CREBBP c.1823+5G>A Pathogenic/Likely pathogenic ★★ same condition
- CREBBP c.3779+1G>T Pathogenic ★★ same condition
- CREBBP p.Arg1378Pro Pathogenic/Likely pathogenic ★★ same condition
- CREBBP p.Arg1392Ter Pathogenic ★★ same condition
- CREBBP p.Arg1867Trp Pathogenic/Likely pathogenic ★★ same condition
- CREBBP p.Arg1868Gln Pathogenic/Likely pathogenic ★★ same condition
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/crebbp-p-arg75ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown