ITPKB p.Ser588=
c.1764C>T · rs56095953 · VCV2688336
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 9.72%, amr) — too common for a highly-penetrant pathogenic allele
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 4.6 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 8.182 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.72%
Admixed American · 5,603/57,616 alleles
Filtering AF
9.51%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.43%
Overall
0.989%
15,802/1,597,684 alleles · common
exomes 13,906/1,445,436 · genomes 1,896/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 9.72% | 10 |
| East Asian | 7.23% | 14 |
| South Asian | 6.11% | 16 |
| Remaining individualsnot grpmax-eligible | 1.12% | 89 |
| Middle Eastern | 0.301% | 332 |
| African / African-American | 0.157% | 637 |
| Finnishnot grpmax-eligible | 0.132% | 758 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0805% | 1,242 |
| European (non-Finnish) | 0.0506% | 1,978 |
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
- ITPKB
- Protein
- p.Ser588=
- Coding
- c.1764C>T
- MANE Select
- NM_002221
- dbSNP
- rs56095953
- Type
- single nucleotide variant
- Location
- chr1:226735695 (GRCh38)
- Gene constraint
- LOEUF 0.34 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 56.58
- Residue 588
- the 'disordered' region
Similar variants
- ITPKB p.Glu906Gln Uncertain significance ★★ ⚠ same type
- ITPKB p.Pro358Ser Uncertain significance ★★ ⚠ same type
- ITPKB p.Pro415His Uncertain significance ★★ ⚠ same type
- ITPKB p.Thr757Ala Uncertain significance ★★ ⚠ same type
- ITPKB c.-8C>T Benign ★★ same type
- ITPKB p.Ala632= Benign ★★ same type
- ITPKB p.Asn592= Benign ★★ same type
- ITPKB p.Asp320Ala Benign/Likely 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/itpkb-p-ser588 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown