Is GATA2 p.Pro368Ser (c.1102C>T) pathogenic?

GATA2 p.Pro368Ser (c.1102C>T) is classified Uncertain significance in GATA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-18). AlphaMissense: likely pathogenic (0.997); Absent from gnomAD v4.1; Associated with deafness-lymphedema-leukemia syndrome.

What condition is associated with GATA2 p.Pro368Ser (c.1102C>T)?

GATA2 p.Pro368Ser (c.1102C>T) is associated with deafness-lymphedema-leukemia syndrome, monocytopenia with susceptibility to infections (ClinVar).

How common is GATA2 p.Pro368Ser (c.1102C>T) in the general population?

GATA2 p.Pro368Ser (c.1102C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GATA2 p.Pro368Ser (c.1102C>T)?

AlphaMissense predicts likely pathogenic (score 0.997) — an in-silico prediction, not a clinical call.

GATA2 p.Pro368Ser

c.1102C>T · rs2068633510 · VCV1463548

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.997 · 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	0.997	likely pathogenic
REVEL	0.892	moderately pathogenic-leaning
SaProt	LLR -10.55	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.34	constrained · MANE · 650 bp · p 7e-08 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Pro368Ser
Coding: c.1102C>T
MANE Select: NM_032638
dbSNP: rs2068633510
Type: single nucleotide variant
Location: chr3:128481860 (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: monocytopenia with susceptibility to infections

Similar variants

GATA2 p.Pro368Arg Likely pathogenic ★ same residue
GATA2 p.Pro368Ala Uncertain significance ★ ⚠ same residue
GATA2 p.Pro368fs Pathogenic ★★ 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-pro368ser (accessed [today's date]).

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