PROK2 p.Ala33=
c.99T>C · rs775415770 · VCV704985
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0367%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP -0.53, phastCons 1 |
| Overall | ||
| CADD | 13.57 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0367%
Admixed American · 22/60,000 alleles
Filtering AF
0.0248%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0209%
Overall
0.00217%
35/1,611,070 alleles · ultra-rare
exomes 16/1,458,832 · genomes 19/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0367% | 2,727 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,913 |
| East Asian | 0.00223% | 44,886 |
| European (non-Finnish) | 0.000425% | 235,459 |
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
- PROK2
- Protein
- p.Ala33=
- Coding
- c.99T>C
- MANE Select
- NM_001126128
- dbSNP
- rs775415770
- Type
- single nucleotide variant
- Location
- chr3:71781590 (GRCh38)
- Gene constraint
- LOEUF 1.052 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 69.22
Similar variants
- PROK2 p.Ala33Pro Uncertain significance ★ ⚠ same residue
- PROK2 p.Arg101Gln Uncertain significance ★★ ⚠ same type
- PROK2 p.Arg101Trp Uncertain significance ★★ ⚠ same type
- PROK2 p.Arg122Gln Uncertain significance ★★ ⚠ same type
- PROK2 p.Asp66Asn Uncertain significance ★★ ⚠ same type
- PROK2 p.Gly62Asp Uncertain significance ★★ ⚠ same type
- PROK2 p.Val29Met Uncertain significance ★★ ⚠ same type
- PROK2 c.285+14G>A Benign ★★ 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/prok2-p-ala33 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown