Is GATA3 p.Ala17Ser (c.49G>T) pathogenic?

GATA3 p.Ala17Ser (c.49G>T) is classified Uncertain significance in GATA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.0835); Very rare (popmax 0.0019%, amr); Associated with Inborn genetic diseases.

What condition is associated with GATA3 p.Ala17Ser (c.49G>T)?

GATA3 p.Ala17Ser (c.49G>T) is associated with Inborn genetic diseases (ClinVar).

How common is GATA3 p.Ala17Ser (c.49G>T) in the general population?

GATA3 p.Ala17Ser (c.49G>T) is very rare (popmax 0.0019%, amr) (gnomAD).

What do computational predictors say about GATA3 p.Ala17Ser (c.49G>T)?

AlphaMissense predicts likely benign (score 0.0835) — an in-silico prediction, not a clinical call.

GATA3 p.Ala17Ser

c.49G>T · VCV4262161

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0835 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0019%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0835	likely benign
REVEL	0.527	indeterminate
SaProt	LLR -6.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 3,162 bp · p 0.16 · regional, not allelic
Overall
CADD	23.4	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 0.0019% Admixed American · 1/52,694 alleles

Overall 0.000128% 2/1,562,514 alleles · very rare exomes 1/1,410,330 · genomes 1/152,184 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0019%	52,694
European (non-Finnish)	8.67e-05%	1,153,804

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.Ala17Ser
Coding: c.49G>T
MANE Select: NM_001002295
Type: single nucleotide variant
Location: chr10:8055704 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.51 · 3 PDB
Residue 17: the 'interaction with tbx21' region; the 'disordered' region

Full GATA3 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

GATA3 p.Ala17= Likely benign ★★ same residue
GATA3 p.Arg299Trp Likely pathogenic ★★ same condition
GATA3 p.Arg86Cys Uncertain significance ★★ ⚠ same condition
GATA3 p.His15Gln Uncertain significance ★★ ⚠ same condition
GATA3 p.Leu190Pro Uncertain significance ★★ ⚠ same condition
GATA3 p.Pro244Ala Uncertain significance ★★ ⚠ same condition
GATA3 p.Thr152Pro Uncertain significance ★★ ⚠ same condition
GATA3 p.Thr418Ile 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-ala17ser (accessed [today's date]).

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