Is GATA4 p.Ser52Pro (c.154T>C) pathogenic?

GATA4 p.Ser52Pro (c.154T>C) is classified Uncertain significance in GATA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-29). AlphaMissense: likely benign (0.0731); No allele count reported in gnomAD v4.1 (AN 1,528,090); Associated with Cardiovascular phenotype.

What condition is associated with GATA4 p.Ser52Pro (c.154T>C)?

GATA4 p.Ser52Pro (c.154T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is GATA4 p.Ser52Pro (c.154T>C) in the general population?

GATA4 p.Ser52Pro (c.154T>C) is no allele count reported in gnomAD v4.1 (AN 1,528,090) (gnomAD).

What do computational predictors say about GATA4 p.Ser52Pro (c.154T>C)?

AlphaMissense predicts likely benign (score 0.0731) — an in-silico prediction, not a clinical call.

GATA4 p.Ser52Pro

c.154T>C · VCV3519060

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0731 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,528,090)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0731	likely benign
REVEL	0.335	indeterminate
SaProt	LLR -6.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.3	GERP -1.6, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 41 kb · p 0.015 · regional, not allelic
Overall
CADD	18.71	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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 1,528,090). 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.Ser52Pro
Coding: c.154T>C
MANE Select: NM_001308093
Type: single nucleotide variant
Location: chr8:11708466 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.64 · 3 PDB
Residue 52: a UniProt-annotated variant site (in asd2)

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

Similar variants

GATA4 p.Ser52= Likely benign ★ same residue
GATA4 p.Ser52Phe Pathogenic same residue
GATA4 c.1001-3C>T Uncertain significance ★★ same condition
GATA4 p.Ala138Gly Uncertain significance ★★ ⚠ same condition
GATA4 p.Ala139Thr Uncertain significance ★★ ⚠ same condition
GATA4 p.Ala155Val Uncertain significance ★★ ⚠ same condition
GATA4 p.Ala171Gly Uncertain significance ★★ ⚠ same condition
GATA4 p.Ala196Thr 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-ser52pro (accessed [today's date]).

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