CTRB1 p.Pro254=
c.762T>A · VCV4821247
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0307%, 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 -0.81 | GERP -4 |
| Overall | ||
| CADD | 4.665 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0307%
South Asian · 28/91,068 alleles
Filtering AF
0.0218%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0188%
Overall
0.00211%
34/1,613,758 alleles · ultra-rare
exomes 33/1,461,570 · genomes 1/152,188 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0307% | 3,252 |
| Middle Eastern | 0.0164% | 6,082 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| European (non-Finnish) | 0.000169% | 590,005 |
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
- CTRB1
- Protein
- p.Pro254=
- Coding
- c.762T>A
- MANE Select
- NM_001906
- Type
- single nucleotide variant
- Location
- chr16:75224836 (GRCh38)
- Gene constraint
- LOEUF 1.902 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.90
- Residue 254
- the peptidase s1 domain
Similar variants
- CTRB1 p.Ala104Asp Uncertain significance ★ ⚠ same type
- CTRB1 p.Ala138Thr Uncertain significance ★ ⚠ same type
- CTRB1 p.Ala144Thr Uncertain significance ★ ⚠ same type
- CTRB1 p.Ala150Ser Uncertain significance ★ ⚠ same type
- CTRB1 p.Ala177Val Uncertain significance ★ ⚠ same type
- CTRB1 p.Ala261Val Uncertain significance ★ ⚠ same type
- CTRB1 p.Ala40Thr Uncertain significance ★ ⚠ same type
- CTRB1 p.Arg131Cys 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/ctrb1-p-pro254 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown