Is GATA4 p.Arg321= (c.963G>A) pathogenic?

GATA4 p.Arg321= (c.963G>A) is classified Likely benign in GATA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-15). Absent from gnomAD v4.1; Associated with atrioventricular septal defect 4.

What condition is associated with GATA4 p.Arg321= (c.963G>A)?

GATA4 p.Arg321= (c.963G>A) is associated with atrioventricular septal defect 4 (ClinVar).

How common is GATA4 p.Arg321= (c.963G>A) in the general population?

GATA4 p.Arg321= (c.963G>A) is absent from gnomAD v4.1 (gnomAD).

GATA4 p.Arg321=

c.963G>A · rs2130338269 · VCV1551774

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	all four deltas below 0.2 · G>T here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.4	GERP 1.9, phastCons 1
Overall
CADD	12.2	PHRED · no single calibrated threshold — expert panels disagree

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: GATA4
Protein: p.Arg321=
Coding: c.963G>A
MANE Select: NM_001308093
dbSNP: rs2130338269
Type: single nucleotide variant
Location: chr8:11755096 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.64 · 3 PDB
Residue 321: the 'disordered' region

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.Arg321Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
GATA4 p.Arg321Trp Conflicting classifications of pathogenicity ★ ⚠ 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-arg321 (accessed [today's date]).

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