Is PIK3CD p.Phe698= (c.2094C>T) pathogenic?

PIK3CD p.Phe698= (c.2094C>T) is classified Benign/Likely benign in PIK3CD (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0739%, nfe); Associated with immunodeficiency 14.

What condition is associated with PIK3CD p.Phe698= (c.2094C>T)?

PIK3CD p.Phe698= (c.2094C>T) is associated with immunodeficiency 14 (ClinVar).

How common is PIK3CD p.Phe698= (c.2094C>T) in the general population?

PIK3CD p.Phe698= (c.2094C>T) is ultra-rare (popmax 0.0739%, nfe) (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.Phe698=

c.2094C>T · rs370548772 · VCV725424

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0739%, nfe)

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 -20	GERP -4.4
Overall
CADD	0.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0739% European (non-Finnish) · 872/1,180,030 alleles

Filtering AF 0.0698% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0682%

Overall 0.0589% 950/1,613,738 alleles · ultra-rare exomes 898/1,461,384 · genomes 52/152,354 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0739%	1,353
Remaining individualsnot grpmax-eligible	0.0416%	2,404
Middle Eastern	0.033%	3,031
African / African-American	0.024%	4,170
Finnishnot grpmax-eligible	0.0205%	4,889
Admixed American	0.0133%	7,504
South Asian	0.011%	9,109
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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.Phe698=
Coding: c.2094C>T
MANE Select: NM_005026
dbSNP: rs370548772
Type: single nucleotide variant
Location: chr1:9722013 (GRCh38)
Gene constraint: LOEUF 0.23 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 20 PDB
Residue 698: an α-helix

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.Phe698Leu 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-phe698 (accessed [today's date]).

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