Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 95%, eas) — too common for a highly-penetrant pathogenic allele
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 -0.56 | GERP -3.1 |
| Overall | ||
| CADD | 8.649 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
95%
East Asian · 37,055/39,004 alleles
Filtering AF
94.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 93.9%
Overall
82.3%
1,249,499/1,517,480 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 95% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 88.6% | 1 |
| South Asian | 88% | 1 |
| Admixed American | 86.1% | 1 |
| Middle Eastern | 83.7% | 1 |
| African / African-American | 83.6% | 1 |
| Remaining individualsnot grpmax-eligible | 83.6% | 1 |
| European (non-Finnish) | 81.1% | 1 |
| Finnishnot grpmax-eligible | 80.7% | 1 |
| Amishnot grpmax-eligible | 77.1% | 1 |
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.Pro417=
- Coding
- c.1251T>G
- MANE Select
- NM_001195129
- dbSNP
- rs2741299
- Type
- single nucleotide variant
- Location
- chr2:232524103 (GRCh38)
- Gene constraint
- LOEUF 1.11 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.35
Similar variants
- 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
- PRSS56 p.Pro354Ala 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-pro417 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown