Is GATA2 p.Pro161Ser (c.481C>T) pathogenic?

GATA2 p.Pro161Ser (c.481C>T) is classified Uncertain significance in GATA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-15). AlphaMissense: likely benign (0.0648); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GATA2 p.Pro161Ser (c.481C>T)?

GATA2 p.Pro161Ser (c.481C>T) is associated with Inborn genetic diseases, deafness-lymphedema-leukemia syndrome, monocytopenia with susceptibility to infections (ClinVar).

How common is GATA2 p.Pro161Ser (c.481C>T) in the general population?

GATA2 p.Pro161Ser (c.481C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about GATA2 p.Pro161Ser (c.481C>T)?

AlphaMissense predicts likely benign (score 0.0648) — an in-silico prediction, not a clinical call.

GATA2 p.Pro161Ser

c.481C>T · rs34799090 · VCV568008

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0648 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0648	likely benign
REVEL	0.364	indeterminate
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.3	GERP 0.65, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,299 bp · p 0.69 · regional, not allelic
Overall
CADD	18.75	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,356 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,611,712 alleles · very rare exomes 2/1,459,444 · genomes 0/152,268 · 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.Pro161Ser
Coding: c.481C>T
MANE Select: NM_032638
dbSNP: rs34799090
Type: single nucleotide variant
Location: chr3:128486117 (GRCh38)
Gene constraint: LOEUF 0.335 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 57.11 · 2 PDB
Residue 161: 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.Pro161Leu Uncertain significance ★★ ⚠ same residue
GATA2 p.Pro161Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
GATA2 p.Pro161fs 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-pro161ser (accessed [today's date]).

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