Is GATA2 p.Pro74Ser (c.220C>T) pathogenic?

GATA2 p.Pro74Ser (c.220C>T) is classified Uncertain significance in GATA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-05-15). AlphaMissense: likely benign (0.0642); Very rare (popmax 8.5e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GATA2 p.Pro74Ser (c.220C>T)?

GATA2 p.Pro74Ser (c.220C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GATA2 p.Pro74Ser (c.220C>T) in the general population?

GATA2 p.Pro74Ser (c.220C>T) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about GATA2 p.Pro74Ser (c.220C>T)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

GATA2 p.Pro74Ser

c.220C>T · VCV4871668

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.426	indeterminate
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,299 bp · p 0.69 · regional, not allelic
Overall
CADD	21.8	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 8.5e-05% European (non-Finnish) · 1/1,177,028 alleles

Overall 6.23e-05% 1/1,605,382 alleles · very rare exomes 1/1,453,012 · genomes 0/152,370 · 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.Pro74Ser
Coding: c.220C>T
MANE Select: NM_032638
Type: single nucleotide variant
Location: chr3:128486812 (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

Similar variants

GATA2 p.Pro74Leu Uncertain significance ★★ ⚠ same residue
GATA2 p.Pro74Ala Uncertain significance ★ ⚠ same residue
GATA2 p.Pro74= Likely benign ★ same residue
GATA2 p.Gln282Ter Pathogenic/Likely pathogenic ★★ same condition
GATA2 c.1017+532T>A Uncertain significance ★★ same condition
GATA2 c.-5C>T Uncertain significance ★★ same condition
GATA2 p.Ala103Val Uncertain significance ★★ ⚠ same condition
GATA2 p.Ala157Gly Uncertain significance ★★ ⚠ 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-pro74ser (accessed [today's date]).

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