Is GATA4 p.Pro306= (c.918C>T) pathogenic?

GATA4 p.Pro306= (c.918C>T) is classified Benign/Likely benign in GATA4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Rare (popmax 0.129%, afr); Associated with atrioventricular septal defect 4.

What condition is associated with GATA4 p.Pro306= (c.918C>T)?

GATA4 p.Pro306= (c.918C>T) is associated with atrioventricular septal defect 4 (ClinVar).

How common is GATA4 p.Pro306= (c.918C>T) in the general population?

GATA4 p.Pro306= (c.918C>T) is rare (popmax 0.129%, afr) (gnomAD).

GATA4 p.Pro306=

c.918C>T · rs147050993 · VCV518736

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.129%, afr)

Conditions

atrioventricular septal defect 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.43	GERP -0.1, phastCons 0.99
Overall
CADD	10.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.129% African / African-American · 97/74,908 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.00632% 102/1,613,746 alleles · rare exomes 43/1,461,586 · genomes 59/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.129%	772
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Admixed American	0.00167%	59,998
European (non-Finnish)	8.48e-05%	1,179,793

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.Pro306=
Coding: c.918C>T
MANE Select: NM_001308093
dbSNP: rs147050993
Type: single nucleotide variant
Location: chr8:11755051 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.64 · 3 PDB
Residue 306: an α-helix

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

Disease context

atrioventricular septal defect 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-pro306 (accessed [today's date]).

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