PI4KB p.Pro518=
c.1554G>A · rs41270706 · VCV2672349
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.858%, 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 -0.22 | GERP -4.6, phastCons 0.027 |
| Overall | ||
| CADD | 10.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.858%
Middle Eastern · 52/6,058 alleles
Filtering AF
0.672%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.606%
Overall
0.421%
6,798/1,614,114 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.858% | 117 |
| European (non-Finnish) | 0.494% | 203 |
| Remaining individualsnot grpmax-eligible | 0.432% | 232 |
| Admixed American | 0.38% | 263 |
| South Asian | 0.259% | 386 |
| African / African-American | 0.104% | 962 |
| Finnishnot grpmax-eligible | 0.089% | 1,123 |
| East Asian | 0.0736% | 1,360 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0642% | 1,558 |
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
- PI4KB
- Protein
- p.Pro518=
- Coding
- c.1554G>A
- MANE Select
- NM_001369623
- dbSNP
- rs41270706
- Type
- single nucleotide variant
- Location
- chr1:151302265 (GRCh38)
- Gene constraint
- LOEUF 0.421 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 72.97 · 20 PDB
Similar variants
- PI4KB p.Ile312Val Uncertain significance ★★ ⚠ same type
- PI4KB p.Tyr175Cys Uncertain significance ★★ ⚠ same type
- PI4KB c.-17G>A Uncertain significance ★ same type
- PI4KB c.-6G>T Uncertain significance ★ same type
- PI4KB p.Ala106Val Uncertain significance ★ ⚠ same type
- PI4KB p.Ala605Gly Uncertain significance ★ ⚠ same type
- PI4KB p.Ala67Val Uncertain significance ★ ⚠ same type
- PI4KB p.Ala95Ser 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/pi4kb-p-pro518 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown