Is GATA1 p.Pro73= (c.219A>G) pathogenic?

GATA1 p.Pro73= (c.219A>G) is classified Pathogenic in GATA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-01). Absent from gnomAD v4.1; Associated with acute megakaryoblastic leukemia in down syndrome.

What condition is associated with GATA1 p.Pro73= (c.219A>G)?

GATA1 p.Pro73= (c.219A>G) is associated with acute megakaryoblastic leukemia in down syndrome (ClinVar).

How common is GATA1 p.Pro73= (c.219A>G) in the general population?

GATA1 p.Pro73= (c.219A>G) is absent from gnomAD v4.1 (gnomAD).

How is Acute megakaryoblastic leukemia inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

GATA1 p.Pro73=

c.219A>G · rs2062674480 · VCV998076

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

acute megakaryoblastic leukemia in down syndrome

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
Pangolin	Δ0.45	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Overall
CADD	18.35	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: GATA1
Protein: p.Pro73=
Coding: c.219A>G
MANE Select: NM_002049
dbSNP: rs2062674480
Type: single nucleotide variant
Location: chrX:48791328 (GRCh38)
Structure: AlphaFold pLDDT 59.48 · 1 PDB

Full GATA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

acute megakaryoblastic leukemia in down syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Acute megakaryoblastic leukemia (Orphanet):

Inheritance: Not applicable
Onset: Adult, Childhood
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

GATA1 p.Pro73Arg Uncertain significance ★ ⚠ same residue
GATA1 p.Pro73Leu Uncertain significance ★ ⚠ same residue
GATA1 p.Ser30Ter Pathogenic ★★ same condition
GATA1 p.Glu39delinsGlyGlyLeuAspAlaAlaAlaSerCysThrAlaProSerThrAlaThrAlaAlaAlaAlaAlaTer Pathogenic ★ same condition
GATA1 c.220+1G>A Pathogenic ★★ same type
GATA1 c.220+2T>C Pathogenic/Likely pathogenic ★★ same type
GATA1 p.Arg216Gln Pathogenic ★★ same type
GATA1 p.Arg216Trp Likely pathogenic ★★ same type

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/gata1-p-pro73 (accessed [today's date]).

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