Is GATA4 p.Phe26Val (c.76T>G) pathogenic?

GATA4 p.Phe26Val (c.76T>G) is classified Uncertain significance in GATA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-17). AlphaMissense: likely pathogenic (0.6438); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with GATA4 p.Phe26Val (c.76T>G)?

GATA4 p.Phe26Val (c.76T>G) is associated with Cardiovascular phenotype (ClinVar).

How common is GATA4 p.Phe26Val (c.76T>G) in the general population?

GATA4 p.Phe26Val (c.76T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GATA4 p.Phe26Val (c.76T>G)?

AlphaMissense predicts likely pathogenic (score 0.6438) — an in-silico prediction, not a clinical call.

GATA4 p.Phe26Val

c.76T>G · rs1554488388 · VCV518676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6438 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.6438	likely pathogenic
REVEL	0.81	moderately pathogenic-leaning
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 41 kb · p 0.015 · regional, not allelic
Overall
CADD	23.9	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

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.Phe26Val
Coding: c.76T>G
MANE Select: NM_001308093
dbSNP: rs1554488388
Type: single nucleotide variant
Location: chr8:11708388 (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

Similar variants

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
GATA4 p.Ala32Thr 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-phe26val (accessed [today's date]).

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