Is PIK3CA p.Pro2= (c.6T>G) pathogenic?

PIK3CA p.Pro2= (c.6T>G) is classified Likely benign in PIK3CA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-17). Very rare (popmax 8.76e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PIK3CA p.Pro2= (c.6T>G)?

PIK3CA p.Pro2= (c.6T>G) is associated with Inborn genetic diseases (ClinVar).

How common is PIK3CA p.Pro2= (c.6T>G) in the general population?

PIK3CA p.Pro2= (c.6T>G) is very rare (popmax 8.76e-05%, nfe) (gnomAD).

PIK3CA p.Pro2=

c.6T>G · rs2473886032 · VCV1756636

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.76e-05%, nfe)

Conditions

Inborn genetic diseases

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 5.1	GERP 0.62, phastCons 1
Overall
CADD	12.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.76e-05% European (non-Finnish) · 1/1,141,088 alleles

Overall 6.52e-05% 1/1,533,294 alleles · very rare exomes 1/1,380,972 · genomes 0/152,322 · joint denominator

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: PIK3CA
Protein: p.Pro2=
Coding: c.6T>G
MANE Select: NM_006218
dbSNP: rs2473886032
Type: single nucleotide variant
Location: chr3:179198831 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.50 · 135 PDB

Full PIK3CA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIK3CA p.Pro2Ser Uncertain significance ★ ⚠ same residue
PIK3CA p.Cys378Arg Pathogenic ★★ ⚠ same condition
PIK3CA p.Glu542Gly Likely pathogenic ★★ ⚠ same condition
PIK3CA p.His1047Leu Pathogenic ★★ same condition
PIK3CA p.Arg401Gln Uncertain significance ★★ ⚠ same condition
PIK3CA p.Arg740Lys Uncertain significance ★★ ⚠ same condition
PIK3CA p.Arg808Trp Uncertain significance ★★ ⚠ same condition
PIK3CA p.Arg899His Uncertain significance ★★ 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/pik3ca-p-pro2 (accessed [today's date]).

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