Is GATA2 p.Val70Phe (c.208G>T) pathogenic?

GATA2 p.Val70Phe (c.208G>T) is classified Conflicting classifications of pathogenicity in GATA2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-18). AlphaMissense: likely benign (0.2565); Ultra-rare (popmax 0.0762%, eas); Associated with GATA2 deficiency with susceptibility to MDS/AML.

What condition is associated with GATA2 p.Val70Phe (c.208G>T)?

GATA2 p.Val70Phe (c.208G>T) is associated with GATA2 deficiency with susceptibility to MDS/AML, deafness-lymphedema-leukemia syndrome, monocytopenia with susceptibility to infections (ClinVar).

How common is GATA2 p.Val70Phe (c.208G>T) in the general population?

GATA2 p.Val70Phe (c.208G>T) is ultra-rare (popmax 0.0762%, eas) (gnomAD).

What do computational predictors say about GATA2 p.Val70Phe (c.208G>T)?

AlphaMissense predicts likely benign (score 0.2565) — an in-silico prediction, not a clinical call.

GATA2 p.Val70Phe

c.208G>T · rs570531959 · VCV472452

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2565 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0762%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

GATA2 deficiency with susceptibility to MDS/AML

Computational evidence

Protein change
AlphaMissense	0.2565	likely benign
REVEL	0.646	pathogenic-leaning
SaProt	LLR -5.87	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,299 bp · p 0.69 · regional, not allelic
Overall
CADD	21.3	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 0.0762% East Asian · 34/44,646 alleles

Filtering AF 0.056% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0491%

Overall 0.00218% 35/1,608,808 alleles · ultra-rare exomes 32/1,456,410 · genomes 3/152,398 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0762%	1,313
Remaining individualsnot grpmax-eligible	0.00161%	62,232

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.Val70Phe
Coding: c.208G>T
MANE Select: NM_032638
dbSNP: rs570531959
Type: single nucleotide variant
Location: chr3:128486824 (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

GATA2 deficiency with susceptibility to MDS/AML — 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 myelodysplastic syndrome

Similar variants

GATA2 p.Val70= Likely benign ★ same residue
GATA2 p.Val70fs 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
GATA2 p.Ala372Thr 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-val70phe (accessed [today's date]).

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