CELA2B p.Pro219=
c.657G>A · VCV3489973
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 -15 | GERP -3.7 |
| Overall | ||
| CADD | 0.234 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.0035%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00318%
Overall
0.00452%
73/1,614,036 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Finnishnot grpmax-eligible | 0.0141% | 7,112 |
| Admixed American | 0.00667% | 15,002 |
| European (non-Finnish) | 0.00449% | 22,265 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| African / African-American | 0.00267% | 37,461 |
| East Asian | 0.00223% | 44,892 |
| South Asian | 0.0011% | 91,082 |
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
- CELA2B
- Protein
- p.Pro219=
- Coding
- c.657G>A
- MANE Select
- NM_015849
- Type
- single nucleotide variant
- Location
- chr1:15487302 (GRCh38)
- Gene constraint
- LOEUF 0.987 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.37
- Residue 219
- a disulfide bond; the peptidase s1 domain
Similar variants
- CELA2B p.His232= Benign ★★ same type
- CELA2B p.Ala128Thr Uncertain significance ★ ⚠ same type
- CELA2B p.Ala14Val Uncertain significance ★ ⚠ same type
- CELA2B p.Ala203Pro Uncertain significance ★ ⚠ same type
- CELA2B p.Arg228Trp Uncertain significance ★ same type
- CELA2B p.Asn129Lys Uncertain significance ★ ⚠ same type
- CELA2B p.Asp226Val Uncertain significance ★ same type
- CELA2B p.Asp25Val 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/cela2b-p-pro219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown