Is GATA4 p.Pro103Ala (c.307C>G) pathogenic?

GATA4 p.Pro103Ala (c.307C>G) is classified Uncertain significance in GATA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-01). AlphaMissense: likely benign (0.0539); No allele count reported in gnomAD v4.1 (AN 1,342,804); Associated with atrioventricular septal defect 4.

What condition is associated with GATA4 p.Pro103Ala (c.307C>G)?

GATA4 p.Pro103Ala (c.307C>G) is associated with atrioventricular septal defect 4 (ClinVar).

How common is GATA4 p.Pro103Ala (c.307C>G) in the general population?

GATA4 p.Pro103Ala (c.307C>G) is no allele count reported in gnomAD v4.1 (AN 1,342,804) (gnomAD).

What do computational predictors say about GATA4 p.Pro103Ala (c.307C>G)?

AlphaMissense predicts likely benign (score 0.0539) — an in-silico prediction, not a clinical call.

GATA4 p.Pro103Ala

c.307C>G · rs1800009849 · VCV2735120

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0539 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,342,804)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

atrioventricular septal defect 4

Computational evidence

Protein change
AlphaMissense	0.0539	likely benign
REVEL	0.756	pathogenic-leaning
SaProt	LLR -5.70	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 1.5, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 41 kb · p 0.015 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,342,804). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GATA4
Protein: p.Pro103Ala
Coding: c.307C>G
MANE Select: NM_001308093
dbSNP: rs1800009849
Type: single nucleotide variant
Location: chr8:11708619 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.64 · 3 PDB
Residue 103: 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.Pro103= Likely benign ★★ same residue
GATA4 p.Pro103Arg 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-pro103ala (accessed [today's date]).

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