PRSS8 p.Ser89=
c.267C>T · rs760018677 · VCV3219964
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0332%, 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 -1.5 | GERP -4.9 |
| Overall | ||
| CADD | 2.017 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0332%
Middle Eastern · 2/6,026 alleles
Filtering AF
0.0116%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00905%
Overall
0.00268%
43/1,603,320 alleles · ultra-rare
exomes 37/1,451,284 · genomes 6/152,036 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0332% | 3,013 |
| Admixed American | 0.0202% | 4,962 |
| South Asian | 0.0111% | 9,022 |
| Remaining individualsnot grpmax-eligible | 0.00484% | 20,659 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00347% | 28,838 |
| African / African-American | 0.00268% | 37,354 |
| Finnishnot grpmax-eligible | 0.0016% | 62,646 |
| European (non-Finnish) | 0.00102% | 97,809 |
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
- PRSS8
- Protein
- p.Ser89=
- Coding
- c.267C>T
- MANE Select
- NM_002773
- dbSNP
- rs760018677
- Type
- single nucleotide variant
- Location
- chr16:31132953 (GRCh38)
- Gene constraint
- LOEUF 0.789 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 84.49 · 9 PDB
- Residue 89
- the peptidase s1 domain
Similar variants
- PRSS8 p.Gly8Glu Benign ★★ same type
- PRSS8 p.Ala160Thr Uncertain significance ★ ⚠ same type
- PRSS8 p.Ala233Thr Uncertain significance ★ same type
- PRSS8 p.Ala278Pro Uncertain significance ★ ⚠ same type
- PRSS8 p.Ala317Gly Uncertain significance ★ ⚠ same type
- PRSS8 p.Ala95Val Uncertain significance ★ ⚠ same type
- PRSS8 p.Arg44Cys Uncertain significance ★ ⚠ same type
- PRSS8 p.Asp237Ala 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/prss8-p-ser89 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown