Is PIK3CD p.Pro299= (c.897G>A) pathogenic?

PIK3CD p.Pro299= (c.897G>A) is classified Likely benign in PIK3CD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-29). Ultra-rare (popmax 0.052%, afr); Associated with immunodeficiency 14.

What condition is associated with PIK3CD p.Pro299= (c.897G>A)?

PIK3CD p.Pro299= (c.897G>A) is associated with immunodeficiency 14 (ClinVar).

How common is PIK3CD p.Pro299= (c.897G>A) in the general population?

PIK3CD p.Pro299= (c.897G>A) is ultra-rare (popmax 0.052%, afr) (gnomAD).

How is Activated PI3K-delta syndrome 1 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PIK3CD p.Pro299=

c.897G>A · rs149279787 · VCV738183

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.052%, afr)

Conditions

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 -11	GERP -3.2
Overall
CADD	0.086	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.052% African / African-American · 39/75,054 alleles

Filtering AF 0.039% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0345%

Overall 0.00403% 65/1,613,972 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.052%	1,924
Admixed American	0.00833%	12,008
Remaining individualsnot grpmax-eligible	0.0048%	20,835
Finnishnot grpmax-eligible	0.0047%	21,273
South Asian	0.00439%	22,772
European (non-Finnish)	0.000932%	107,274

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: PIK3CD
Protein: p.Pro299=
Coding: c.897G>A
MANE Select: NM_005026
dbSNP: rs149279787
Type: single nucleotide variant
Location: chr1:9717075 (GRCh38)
Gene constraint: LOEUF 0.23 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 20 PDB
Residue 299: the 'disordered' region

Full PIK3CD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Activated PI3K-delta syndrome 1 (Orphanet):

Inheritance: Autosomal dominant

Similar variants

PIK3CD p.Pro299Leu Uncertain significance ★ ⚠ same residue
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

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-pro299 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown