Is GATA2 p.Pro461= (c.1383C>T) pathogenic?

GATA2 p.Pro461= (c.1383C>T) is classified Likely benign in GATA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-20). Very rare (popmax 0.00221%, sas); Associated with Inborn genetic diseases.

What condition is associated with GATA2 p.Pro461= (c.1383C>T)?

GATA2 p.Pro461= (c.1383C>T) is associated with Inborn genetic diseases, deafness-lymphedema-leukemia syndrome, monocytopenia with susceptibility to infections (ClinVar).

How common is GATA2 p.Pro461= (c.1383C>T) in the general population?

GATA2 p.Pro461= (c.1383C>T) is very rare (popmax 0.00221%, sas) (gnomAD).

GATA2 p.Pro461=

c.1383C>T · rs1200504281 · VCV1593042

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

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 0.025	GERP -3.2, phastCons 0.23
Overall
CADD	2.944	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% South Asian · 2/90,452 alleles

Filtering AF 0.000367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000124% 2/1,607,638 alleles · very rare exomes 2/1,455,276 · genomes 0/152,362 · 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: GATA2
Protein: p.Pro461=
Coding: c.1383C>T
MANE Select: NM_032638
dbSNP: rs1200504281
Type: single nucleotide variant
Location: chr3:128481079 (GRCh38)
Gene constraint: LOEUF 0.335 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.11 · 2 PDB
Residue 461: the 'disordered' region

Full GATA2 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

Also linked: deafness-lymphedema-leukemia syndrome monocytopenia with susceptibility to infections

Similar variants

GATA2 p.Pro461Ala Uncertain significance ★★ ⚠ same residue
GATA2 p.Pro461Ser Uncertain significance ★★ same residue
GATA2 p.Pro461Thr Uncertain significance ★ ⚠ same residue
GATA2 c.1017+572C>T Pathogenic/Likely pathogenic ★★ same condition
GATA2 c.1018-1G>T Pathogenic/Likely pathogenic ★★ same condition
GATA2 c.1018-2A>G Pathogenic/Likely pathogenic ★★ same condition
GATA2 c.1018-2A>T Pathogenic ★★ same condition
GATA2 c.1143+2T>A Pathogenic/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/gata2-p-pro461 (accessed [today's date]).

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