Is GATA3 p.Val72= (c.216G>T) pathogenic?

GATA3 p.Val72= (c.216G>T) is classified Benign/Likely benign in GATA3 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-11-13). Rare (popmax 0.431%, sas); Associated with hypoparathyroidism-deafness-renal disease syndrome.

What condition is associated with GATA3 p.Val72= (c.216G>T)?

GATA3 p.Val72= (c.216G>T) is associated with hypoparathyroidism-deafness-renal disease syndrome (ClinVar).

How common is GATA3 p.Val72= (c.216G>T) in the general population?

GATA3 p.Val72= (c.216G>T) is rare (popmax 0.431%, sas) (gnomAD).

GATA3 p.Val72=

c.216G>T · rs560531559 · VCV301119

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.431%, sas)

Conditions

hypoparathyroidism-deafness-renal disease syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 1.4, phastCons 1
Overall
CADD	15.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.431% South Asian · 368/85,396 alleles

Filtering AF 0.395% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.38%

Overall 0.031% 486/1,568,256 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.431%	232
Middle Eastern	0.399%	251
Remaining individualsnot grpmax-eligible	0.0511%	1,959
Admixed American	0.0167%	5,985
European (non-Finnish)	0.0045%	22,238
East Asian	0.00237%	42,112
African / African-American	0.00135%	73,852

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: GATA3
Protein: p.Val72=
Coding: c.216G>T
MANE Select: NM_001002295
dbSNP: rs560531559
Type: single nucleotide variant
Location: chr10:8055871 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.51 · 3 PDB
Residue 72: the 'interaction with tbx21' region

Full GATA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypoparathyroidism-deafness-renal disease syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GATA3 p.Val72Ala Uncertain significance ★★ ⚠ same residue
GATA3 c.1050+2T>C Pathogenic ★★ same condition
GATA3 c.924+1G>A Pathogenic/Likely pathogenic ★★ same condition
GATA3 p.Arg276Gln Pathogenic/Likely pathogenic ★★ same condition
GATA3 p.Arg299Gln Pathogenic/Likely pathogenic ★★ same condition
GATA3 p.Arg306Ter Pathogenic ★★ same condition
GATA3 p.Arg367Ter Pathogenic ★★ same condition
GATA3 p.Ser166Ter 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/gata3-p-val72 (accessed [today's date]).

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