Is GATA3 p.Phe153Leu (c.459C>G) pathogenic?

GATA3 p.Phe153Leu (c.459C>G) is classified Uncertain significance in GATA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). AlphaMissense: likely pathogenic (0.9838); Absent from gnomAD v4.1; Associated with hypoparathyroidism-deafness-renal disease syndrome.

What condition is associated with GATA3 p.Phe153Leu (c.459C>G)?

GATA3 p.Phe153Leu (c.459C>G) is associated with hypoparathyroidism-deafness-renal disease syndrome (ClinVar).

How common is GATA3 p.Phe153Leu (c.459C>G) in the general population?

GATA3 p.Phe153Leu (c.459C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GATA3 p.Phe153Leu (c.459C>G)?

AlphaMissense predicts likely pathogenic (score 0.9838) — an in-silico prediction, not a clinical call.

GATA3 p.Phe153Leu

c.459C>G · VCV3598269

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9838 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hypoparathyroidism-deafness-renal disease syndrome

Computational evidence

Protein change
AlphaMissense	0.9838	likely pathogenic
REVEL	0.621	indeterminate
SaProt	LLR -10.43	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.35	GERP -2.6, phastCons 0.088
Regional constraint	o/e 1.08	unconstrained · MANE · 3,162 bp · p 0.16 · regional, not allelic
Overall
CADD	17.37	PHRED · no single calibrated threshold — expert panels disagree

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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GATA3
Protein: p.Phe153Leu
Coding: c.459C>G
MANE Select: NM_001002295
Type: single nucleotide variant
Location: chr10:8058522 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.51 · 3 PDB
Residue 153: the 'interaction with tbx21' region; the 'disordered' 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 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
GATA3 p.Arg202His 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/gata3-p-phe153leu (accessed [today's date]).

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