Is GATA2 p.Pro87Ser (c.259C>T) pathogenic?

GATA2 p.Pro87Ser (c.259C>T) is classified Uncertain significance in GATA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-05). AlphaMissense: likely pathogenic (0.6485); Very rare (popmax 8.49e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GATA2 p.Pro87Ser (c.259C>T)?

GATA2 p.Pro87Ser (c.259C>T) is associated with Inborn genetic diseases, deafness-lymphedema-leukemia syndrome, monocytopenia with susceptibility to infections (ClinVar).

How common is GATA2 p.Pro87Ser (c.259C>T) in the general population?

GATA2 p.Pro87Ser (c.259C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about GATA2 p.Pro87Ser (c.259C>T)?

AlphaMissense predicts likely pathogenic (score 0.6485) — an in-silico prediction, not a clinical call.

GATA2 p.Pro87Ser

c.259C>T · rs1260113676 · VCV2062407

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6485 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6485	likely pathogenic
REVEL	0.768	pathogenic-leaning
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 0.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,299 bp · p 0.69 · regional, not allelic
Overall
CADD	25.0	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

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,448 alleles

Overall 6.24e-05% 1/1,602,254 alleles · very rare exomes 1/1,450,030 · genomes 0/152,224 · 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.Pro87Ser
Coding: c.259C>T
MANE Select: NM_032638
dbSNP: rs1260113676
Type: single nucleotide variant
Location: chr3:128486339 (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

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 acute myeloid leukemia

Similar variants

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
GATA2 p.Ala372Thr Likely pathogenic ★★ same condition
GATA2 p.Arg204Ter Pathogenic ★★ same condition
GATA2 p.Arg330Ter 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-pro87ser (accessed [today's date]).

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