Is GATA3 p.Pro191= (c.573C>T) pathogenic?

GATA3 p.Pro191= (c.573C>T) is classified Benign in GATA3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Low-frequency (popmax 3.7%, mid); Associated with hypoparathyroidism-deafness-renal disease syndrome.

What condition is associated with GATA3 p.Pro191= (c.573C>T)?

GATA3 p.Pro191= (c.573C>T) is associated with hypoparathyroidism-deafness-renal disease syndrome (ClinVar).

How common is GATA3 p.Pro191= (c.573C>T) in the general population?

GATA3 p.Pro191= (c.573C>T) is low-frequency (popmax 3.7%, mid) (gnomAD).

GATA3 p.Pro191=

c.573C>T · rs35508267 · VCV301122

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.7%, mid)

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 -7.3	GERP -3.5
Overall
CADD	6.407	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.7% Middle Eastern · 224/6,062 alleles

Filtering AF 3.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.15%

Overall 0.579% 9,342/1,612,860 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	3.7%	27
Ashkenazi Jewishnot grpmax-eligible	3.21%	31
South Asian	2.92%	34
Remaining individualsnot grpmax-eligible	0.907%	110
Admixed American	0.465%	215
European (non-Finnish)	0.381%	262
Finnishnot grpmax-eligible	0.191%	524
African / African-American	0.0533%	1,876
East Asian	0.0111%	8,971

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.Pro191=
Coding: c.573C>T
MANE Select: NM_001002295
dbSNP: rs35508267
Type: single nucleotide variant
Location: chr10:8058636 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.51 · 3 PDB
Residue 191: 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.Pro191Leu 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-pro191 (accessed [today's date]).

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