Is PIK3CD p.Pro97= (c.291C>T) pathogenic?

PIK3CD p.Pro97= (c.291C>T) is classified Likely benign in PIK3CD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-12). Ultra-rare (popmax 0.0164%, mid); Associated with immunodeficiency 14.

What condition is associated with PIK3CD p.Pro97= (c.291C>T)?

PIK3CD p.Pro97= (c.291C>T) is associated with immunodeficiency 14 (ClinVar).

How common is PIK3CD p.Pro97= (c.291C>T) in the general population?

PIK3CD p.Pro97= (c.291C>T) is ultra-rare (popmax 0.0164%, mid) (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.Pro97=

c.291C>T · rs371336444 · VCV1585711

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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	0.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00174% 28/1,613,540 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.012%	8,328
South Asian	0.00659%	15,180
East Asian	0.00445%	22,452
European (non-Finnish)	0.000847%	118,004

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.Pro97=
Coding: c.291C>T
MANE Select: NM_005026
dbSNP: rs371336444
Type: single nucleotide variant
Location: chr1:9715690 (GRCh38)
Gene constraint: LOEUF 0.23 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 20 PDB
Residue 97: the pi3k-abd domain; a β-strand

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.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-pro97 (accessed [today's date]).

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