PRSS56 p.Pro599=
c.1797C>A · rs774483044 · VCV2850654
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00418%, amr)
Conditions
1
isolated microphthalmia 6
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 -0.94 | GERP -2.6 |
| Overall | ||
| CADD | 0.259 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00418%
Admixed American · 2/47,804 alleles
Filtering AF
0.00117%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000948%
Overall
0.00154%
23/1,492,982 alleles · very rare
exomes 22/1,340,910 · genomes 1/152,072 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00418% | 23,902 |
| European (non-Finnish) | 0.00179% | 55,996 |
| Remaining individualsnot grpmax-eligible | 0.00173% | 57,934 |
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
- PRSS56
- Protein
- p.Pro599=
- Coding
- c.1797C>A
- MANE Select
- NM_001195129
- dbSNP
- rs774483044
- Type
- single nucleotide variant
- Location
- chr2:232525491 (GRCh38)
- Gene constraint
- LOEUF 1.11 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.35
- Residue 599
- a UniProt-annotated variant site (in mcop6); the 'disordered' region
Similar variants
- PRSS56 p.Pro599Ala Benign ★★ same residue
- PRSS56 p.Ala502Thr Uncertain significance ★★ ⚠ same condition
- PRSS56 p.Ala57Val Uncertain significance ★★ ⚠ same condition
- PRSS56 p.Ala600Thr Uncertain significance ★★ ⚠ same condition
- PRSS56 p.Arg247Cys Uncertain significance ★★ ⚠ same condition
- PRSS56 p.Asp254Asn Uncertain significance ★★ ⚠ same condition
- PRSS56 p.Gly538Ser Uncertain significance ★★ ⚠ same condition
- PRSS56 p.Leu483Phe Uncertain significance ★★ ⚠ 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/prss56-p-pro599 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown