Is FLT4 p.Pro30fs (c.89del) pathogenic?

FLT4 p.Pro30fs (c.89del) is classified Pathogenic in FLT4 (ClinVar, Single submitter, 2 submitters; last evaluated 2020-06-10). Very rare (popmax 8.48e-05%, nfe); Associated with congenital heart defects, multiple types, 7.

What condition is associated with FLT4 p.Pro30fs (c.89del)?

FLT4 p.Pro30fs (c.89del) is associated with congenital heart defects, multiple types, 7 (ClinVar).

How common is FLT4 p.Pro30fs (c.89del) in the general population?

FLT4 p.Pro30fs (c.89del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

FLT4 p.Pro30fs

c.89del · rs755445139 · VCV812612

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

congenital heart defects, multiple types, 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 30
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -9.1	GERP -2.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,756 alleles

Overall 0.000892% 13/1,458,058 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0198%	5,044
European (non-Finnish)grpmax	8.48e-05%	1,179,756

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: FLT4
Protein: p.Pro30fs
Coding: c.89del
MANE Select: NM_182925
dbSNP: rs755445139
Type: Deletion
Location: chr5:180631748 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 30: the ig-like c2-type 1 domain

Full FLT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital heart defects, multiple types, 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLT4 p.Glu100fs Pathogenic/Likely pathogenic ★★ same condition
FLT4 p.Gly975fs Likely pathogenic ★ same condition
FLT4 p.Pro30Leu Uncertain significance ★ ⚠ same residue
FLT4 c.3332-356_3894-1373del Pathogenic same condition
FLT4 p.Arg318Ter Pathogenic/Likely pathogenic ★★ same condition
FLT4 p.Pro1137Leu Likely pathogenic ★★ same condition
FLT4 p.Arg1060Gln Uncertain significance ★★ ⚠ same condition
FLT4 p.Met1260Leu 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/flt4-p-pro30fs (accessed [today's date]).

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