Is GATA4 p.Ser263= (c.789C>T) pathogenic?

GATA4 p.Ser263= (c.789C>T) is classified Likely benign in GATA4 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-11). Ultra-rare (popmax 0.0401%, eas); Associated with Cardiovascular phenotype.

What condition is associated with GATA4 p.Ser263= (c.789C>T)?

GATA4 p.Ser263= (c.789C>T) is associated with Cardiovascular phenotype, atrioventricular septal defect 4 (ClinVar).

How common is GATA4 p.Ser263= (c.789C>T) in the general population?

GATA4 p.Ser263= (c.789C>T) is ultra-rare (popmax 0.0401%, eas) (gnomAD).

GATA4 p.Ser263=

c.789C>T · rs777744927 · VCV1138267

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -20	GERP -3.8
Overall
CADD	0.011	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0401% East Asian · 18/44,900 alleles

Filtering AF 0.0293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0258%

Overall 0.00669% 108/1,613,972 alleles · ultra-rare exomes 101/1,461,732 · genomes 7/152,240 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0401%	2,494
South Asian	0.0395%	2,530
Remaining individualsnot grpmax-eligible	0.024%	4,166
African / African-American	0.004%	24,982
European (non-Finnish)	0.00297%	33,716
Admixed American	0.00167%	60,004

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: GATA4
Protein: p.Ser263=
Coding: c.789C>T
MANE Select: NM_001308093
dbSNP: rs777744927
Type: single nucleotide variant
Location: chr8:11750113 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.64 · 3 PDB

Full GATA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atrioventricular septal defect 4

Similar variants

GATA4 p.Arg231Ter Pathogenic ★★ same condition
GATA4 p.Arg284His Pathogenic/Likely pathogenic ★★ same condition
GATA4 p.Gly297Ser Pathogenic/Likely pathogenic ★★ same condition
GATA4 c.1001-3C>T Uncertain significance ★★ same condition
GATA4 c.912+5G>A Uncertain significance ★★ same condition
GATA4 c.913-5T>G Uncertain significance ★★ same condition
GATA4 p.Ala131Gly Uncertain significance ★★ ⚠ same condition
GATA4 p.Ala138Glu 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/gata4-p-ser263 (accessed [today's date]).

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