Is PIK3CA p.Leu1026Val (c.3076C>G) pathogenic?

PIK3CA p.Leu1026Val (c.3076C>G) is classified Uncertain significance in PIK3CA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-27). AlphaMissense: likely pathogenic (0.8837); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PIK3CA p.Leu1026Val (c.3076C>G)?

PIK3CA p.Leu1026Val (c.3076C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PIK3CA p.Leu1026Val (c.3076C>G) in the general population?

PIK3CA p.Leu1026Val (c.3076C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PIK3CA p.Leu1026Val (c.3076C>G)?

AlphaMissense predicts likely pathogenic (score 0.8837) — an in-silico prediction, not a clinical call.

PIK3CA p.Leu1026Val

c.3076C>G · rs2108429587 · VCV2587511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8837 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8837	likely pathogenic
REVEL	0.721	pathogenic-leaning
SaProt	LLR -12.99	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 0.13	GERP -2.6, phastCons 0.06
Regional constraint	o/e 0.16	constrained · MANE · 189 bp · p 3e-13 · regional, not allelic
Overall
CADD	21.3	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: PIK3CA
Protein: p.Leu1026Val
Coding: c.3076C>G
MANE Select: NM_006218
dbSNP: rs2108429587
Type: single nucleotide variant
Location: chr3:179234233 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.50 · 135 PDB
Residue 1026: a turn; the pi3k/pi4k catalytic domain

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.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
PIK3CA p.Asn212Ser 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-leu1026val (accessed [today's date]).

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