Is GATA4 p.Ser352= (c.1056C>T) pathogenic?

GATA4 p.Ser352= (c.1056C>T) is classified Likely benign in GATA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-24). Very rare (popmax 0.000169%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with GATA4 p.Ser352= (c.1056C>T)?

GATA4 p.Ser352= (c.1056C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is GATA4 p.Ser352= (c.1056C>T) in the general population?

GATA4 p.Ser352= (c.1056C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

GATA4 p.Ser352=

c.1056C>T · rs1802606371 · VCV1777845

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 1.5, phastCons 1
Overall
CADD	10.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,056 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,260 alleles · very rare exomes 2/1,461,882 · genomes 0/152,378 · 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.Ser352=
Coding: c.1056C>T
MANE Select: NM_001308093
dbSNP: rs1802606371
Type: single nucleotide variant
Location: chr8:11756990 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.64 · 3 PDB
Residue 352: the 'disordered' region

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.Ser352Gly Uncertain significance ★ ⚠ 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
GATA4 p.Ala264Ser 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-ser352 (accessed [today's date]).

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