Is FLT4 p.Arg642fs (c.1925del) pathogenic?

FLT4 p.Arg642fs (c.1925del) is classified Likely pathogenic in FLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-10). Absent from gnomAD; Associated with FLT4-related disorder.

What condition is associated with FLT4 p.Arg642fs (c.1925del)?

FLT4 p.Arg642fs (c.1925del) is associated with FLT4-related disorder (ClinVar).

How common is FLT4 p.Arg642fs (c.1925del) in the general population?

FLT4 p.Arg642fs (c.1925del) is absent from gnomAD (gnomAD).

FLT4 p.Arg642fs

c.1925del · rs2480922403 · VCV2633187

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

FLT4-related disorder

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 13 of 30
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2	GERP -2.6

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FLT4
Protein: p.Arg642fs
Coding: c.1925del
MANE Select: NM_182925
dbSNP: rs2480922403
Type: Deletion
Location: chr5:180621637 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 642: the ig-like c2-type 6 domain; a disulfide bond; a UniProt-annotated variant site (in chtd7)

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

Disease context

FLT4-related disorder

Similar variants

FLT4 p.Glu100fs Pathogenic/Likely pathogenic ★★ same condition
FLT4 p.Asn538fs Likely pathogenic ★ same condition
FLT4 p.Gly744fs Likely pathogenic ★ same condition
FLT4 p.Leu939fs Pathogenic ★ same condition
FLT4 p.Trp711del Uncertain significance ★ same condition
FLT4 p.Gly857Arg Pathogenic ★★ same condition
FLT4 p.Pro1137Leu Likely pathogenic ★★ same condition
FLT4 p.Ser393Arg 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-arg642fs (accessed [today's date]).

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