Is PIK3CA p.Val73= (c.219T>A) pathogenic?

PIK3CA p.Val73= (c.219T>A) is classified Likely benign in PIK3CA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-14). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PIK3CA p.Val73= (c.219T>A)?

PIK3CA p.Val73= (c.219T>A) is associated with Inborn genetic diseases (ClinVar).

How common is PIK3CA p.Val73= (c.219T>A) in the general population?

PIK3CA p.Val73= (c.219T>A) is absent from gnomAD v4.1 (gnomAD).

PIK3CA p.Val73=

c.219T>A · VCV4627640

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 1.2	GERP -0.69, phastCons 1
Overall
CADD	7.253	PHRED · no single calibrated threshold — expert panels disagree

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.Val73=
Coding: c.219T>A
MANE Select: NM_006218
Type: single nucleotide variant
Location: chr3:179199044 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 92.50 · 135 PDB
Residue 73: the pi3k-abd domain; a β-strand

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-val73 (accessed [today's date]).

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