Is GATA6 p.Phe263= (c.789C>T) pathogenic?

GATA6 p.Phe263= (c.789C>T) is classified Likely benign in GATA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). Very rare (popmax 0.00363%, eas); Associated with atrioventricular septal defect 5.

What condition is associated with GATA6 p.Phe263= (c.789C>T)?

GATA6 p.Phe263= (c.789C>T) is associated with atrioventricular septal defect 5 (ClinVar).

How common is GATA6 p.Phe263= (c.789C>T) in the general population?

GATA6 p.Phe263= (c.789C>T) is very rare (popmax 0.00363%, eas) (gnomAD).

GATA6 p.Phe263=

c.789C>T · rs1254802999 · VCV1574424

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00363%, eas)

Conditions

atrioventricular septal defect 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1	GERP -0.7, phastCons 1
Overall
CADD	11.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00363% East Asian · 1/27,536 alleles

Overall 8.41e-05% 1/1,188,628 alleles · very rare exomes 0/1,038,696 · genomes 1/149,932 · 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: GATA6
Protein: p.Phe263=
Coding: c.789C>T
MANE Select: NM_005257
dbSNP: rs1254802999
Type: single nucleotide variant
Location: chr18:22171933 (GRCh38)
Gene constraint: LOEUF 0.527 · pLI 0.95 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.48

Full GATA6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

atrioventricular septal defect 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GATA6 c.1135+2T>C Likely pathogenic ★★ same condition
GATA6 p.Arg456Cys Pathogenic ★★ same condition
GATA6 p.Arg493Ter Pathogenic ★★ same condition
GATA6 p.Ala122Ser Uncertain significance ★★ ⚠ same condition
GATA6 p.Ala122Thr Uncertain significance ★★ ⚠ same condition
GATA6 p.Ala124Thr Uncertain significance ★★ ⚠ same condition
GATA6 p.Ala134Asp Uncertain significance ★★ ⚠ same condition
GATA6 p.Ala134Thr 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/gata6-p-phe263 (accessed [today's date]).

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