Is GATA4 p.Phe154= (c.462C>T) pathogenic?

GATA4 p.Phe154= (c.462C>T) is classified Benign/Likely benign in GATA4 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-28). Rare (popmax 0.44%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with GATA4 p.Phe154= (c.462C>T)?

GATA4 p.Phe154= (c.462C>T) is associated with Cardiovascular phenotype, atrioventricular septal defect 4 (ClinVar).

How common is GATA4 p.Phe154= (c.462C>T) in the general population?

GATA4 p.Phe154= (c.462C>T) is rare (popmax 0.44%, nfe) (gnomAD).

GATA4 p.Phe154=

c.462C>T · rs56348550 · VCV412733

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.44%, 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 3	GERP 0.83, phastCons 1
Overall
CADD	15.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.44% European (non-Finnish) · 4,838/1,099,560 alleles

Filtering AF 0.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.425%

Overall 0.364% 5,221/1,435,180 alleles · rare exomes 4,887/1,283,534 · genomes 334/151,646 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.44%	227
Remaining individualsnot grpmax-eligible	0.329%	304
Finnishnot grpmax-eligible	0.272%	368
African / African-American	0.0759%	1,317
Middle Eastern	0.0741%	1,349
Admixed American	0.0532%	1,880
Ashkenazi Jewishnot grpmax-eligible	0.0408%	2,449
South Asian	0.00421%	23,769

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.Phe154=
Coding: c.462C>T
MANE Select: NM_001308093
dbSNP: rs56348550
Type: single nucleotide variant
Location: chr8:11708774 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: atrioventricular septal defect 4

Similar variants

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
GATA4 p.Ala131Gly Uncertain significance ★★ ⚠ same condition
GATA4 p.Ala138Glu 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-phe154 (accessed [today's date]).

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