Is PIK3CD p.Pro385Ser (c.1153C>T) pathogenic?

PIK3CD p.Pro385Ser (c.1153C>T) is classified Uncertain significance in PIK3CD (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-24). AlphaMissense: likely pathogenic (0.9542); Absent from gnomAD v4.1; Associated with immunodeficiency 14.

What condition is associated with PIK3CD p.Pro385Ser (c.1153C>T)?

PIK3CD p.Pro385Ser (c.1153C>T) is associated with immunodeficiency 14 (ClinVar).

How common is PIK3CD p.Pro385Ser (c.1153C>T) in the general population?

PIK3CD p.Pro385Ser (c.1153C>T) is absent from gnomAD v4.1 (gnomAD).

How is Activated PI3K-delta syndrome 1 inherited?

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

What do computational predictors say about PIK3CD p.Pro385Ser (c.1153C>T)?

AlphaMissense predicts likely pathogenic (score 0.9542) — an in-silico prediction, not a clinical call.

PIK3CD p.Pro385Ser

c.1153C>T · rs2100908773 · VCV1425491

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9542 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 14

Computational evidence

Protein change
AlphaMissense	0.9542	likely pathogenic
REVEL	0.893	moderately pathogenic-leaning
SaProt	LLR -10.40	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 11 kb · p 2.5e-27 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Pro385Ser
Coding: c.1153C>T
MANE Select: NM_005026
dbSNP: rs2100908773
Type: single nucleotide variant
Location: chr1:9718826 (GRCh38)
Gene constraint: LOEUF 0.23 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.21 · 20 PDB
Residue 385: the c2 pi3k-type domain

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-pro385ser (accessed [today's date]).

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