Is GATA2 p.Arg362Pro (c.1085G>C) pathogenic?

GATA2 p.Arg362Pro (c.1085G>C) is classified Likely pathogenic in GATA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-29). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with deafness-lymphedema-leukemia syndrome.

What condition is associated with GATA2 p.Arg362Pro (c.1085G>C)?

GATA2 p.Arg362Pro (c.1085G>C) is associated with deafness-lymphedema-leukemia syndrome, GATA2 deficiency with susceptibility to MDS/AML (ClinVar).

How common is GATA2 p.Arg362Pro (c.1085G>C) in the general population?

GATA2 p.Arg362Pro (c.1085G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GATA2 p.Arg362Pro (c.1085G>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

GATA2 p.Arg362Pro

c.1085G>C · rs867160952 · VCV1184157

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

deafness-lymphedema-leukemia syndrome

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 9% in GATA2
REVEL	0.978	strongly pathogenic-leaning
SaProt	LLR -13.76	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 650 bp · p 7e-08 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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: GATA2
Protein: p.Arg362Pro
Coding: c.1085G>C
MANE Select: NM_032638
dbSNP: rs867160952
Type: single nucleotide variant
Location: chr3:128481877 (GRCh38)
Gene constraint: LOEUF 0.335 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.11 · 2 PDB

Full GATA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

deafness-lymphedema-leukemia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: GATA2 deficiency with susceptibility to MDS/AML

Similar variants

GATA2 p.Arg362Ter Pathogenic/Likely pathogenic ★★ same residue
GATA2 p.Arg362Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
GATA2 p.Arg362= Likely benign ★ same residue
GATA2 p.Arg362_Asn365del Likely pathogenic ★ same residue
GATA2 p.Arg362fs Pathogenic ★ same residue
GATA2 p.Arg362_Asn363insArgAlaGlyThrCysCysAlaAsnCysGlnThrThrThrThrThrLeuTrpArgArg Uncertain significance ★ same residue
GATA2 p.Arg362dup Conflicting classifications of pathogenicity ★ same residue
GATA2 p.Arg362Gly Uncertain significance ★ ⚠ same residue

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-arg362pro (accessed [today's date]).

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