PIK3CD p.Phe751=
c.2253C>T · VCV4721890
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
immunodeficiency 14
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 2.6 | GERP 0.7, phastCons 1 |
| Overall | ||
| CADD | 12.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PIK3CD
- Protein
- p.Phe751=
- Coding
- c.2253C>T
- MANE Select
- NM_005026
- Type
- single nucleotide variant
- Location
- chr1:9722262 (GRCh38)
- Gene constraint
- LOEUF 0.23 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 88.21 · 20 PDB
- Residue 751
- a UniProt-annotated variant site (in rochis; no protein can be detected by western blot in patient cells); the pi3k/pi4k catalytic domain; the 'g-loop' region
Disease context
immunodeficiency 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Activated PI3K-delta syndrome 1 (Orphanet):
- Inheritance
- Autosomal dominant
Similar variants
- PIK3CD p.Asn334Lys Likely pathogenic ★★★ ⚠ same condition
- PIK3CD p.Glu1021Lys Pathogenic ★★★ ⚠ same condition
- PIK3CD p.Glu1025Gly Pathogenic ★★★ ⚠ same condition
- PIK3CD p.Glu525Ala Likely pathogenic ★★★ ⚠ same condition
- PIK3CD p.Glu525Gly Likely pathogenic ★★★ ⚠ same condition
- PIK3CD p.Glu525Lys Pathogenic ★★★ ⚠ same condition
- PIK3CD p.Glu81Lys Likely pathogenic ★★★ same condition
- PIK3CD p.Gly124Asp Likely pathogenic ★★★ ⚠ 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/pik3cd-p-phe751 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown