Is GATA4 p.Pro40= (c.120C>T) pathogenic?

GATA4 p.Pro40= (c.120C>T) is classified Likely benign in GATA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). Very rare (popmax 0.00119%, sas); Associated with atrioventricular septal defect 4.

What condition is associated with GATA4 p.Pro40= (c.120C>T)?

GATA4 p.Pro40= (c.120C>T) is associated with atrioventricular septal defect 4 (ClinVar).

How common is GATA4 p.Pro40= (c.120C>T) in the general population?

GATA4 p.Pro40= (c.120C>T) is very rare (popmax 0.00119%, sas) (gnomAD).

GATA4 p.Pro40=

c.120C>T · VCV3658289

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Conditions

atrioventricular septal defect 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.104	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 0.57, phastCons 1
Overall
CADD	12.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% South Asian · 1/84,096 alleles

Overall 6.51e-05% 1/1,535,120 alleles · very rare exomes 1/1,382,954 · genomes 0/152,166 · joint denominator

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.Pro40=
Coding: c.120C>T
MANE Select: NM_001308093
Type: single nucleotide variant
Location: chr8:11708432 (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

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

Similar variants

GATA4 p.Pro40Ser Uncertain significance ★★ ⚠ same residue
GATA4 p.Pro40Leu Uncertain significance ★ ⚠ same residue
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

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-pro40 (accessed [today's date]).

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