Is FLT4 p.Leu192= (c.576C>T) pathogenic?

FLT4 p.Leu192= (c.576C>T) is classified Likely benign in FLT4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-03-11). Ultra-rare (popmax 0.0624%, eas); Associated with FLT4-related disorder.

What condition is associated with FLT4 p.Leu192= (c.576C>T)?

FLT4 p.Leu192= (c.576C>T) is associated with FLT4-related disorder (ClinVar).

How common is FLT4 p.Leu192= (c.576C>T) in the general population?

FLT4 p.Leu192= (c.576C>T) is ultra-rare (popmax 0.0624%, eas) (gnomAD).

FLT4 p.Leu192=

c.576C>T · rs140192529 · VCV3031493

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0624%, eas)

Conditions

FLT4-related disorder

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 -2.8	GERP -3.2
Overall
CADD	5.045	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0624% East Asian · 28/44,878 alleles

Filtering AF 0.0443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0382%

Overall 0.00316% 51/1,612,772 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0624%	1,603
Middle Eastern	0.0165%	6,058
African / African-American	0.016%	6,253
Remaining individualsnot grpmax-eligible	0.0048%	20,830
European (non-Finnish)	0.000593%	168,571

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.Leu192=
Coding: c.576C>T
MANE Select: NM_182925
dbSNP: rs140192529
Type: single nucleotide variant
Location: chr5:180630043 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 192: a disulfide bond; a UniProt-annotated variant site (in chtd7); the ig-like c2-type 2 domain

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

Disease context

FLT4-related disorder

Similar variants

FLT4 p.Gly857Arg Pathogenic ★★ same condition
FLT4 p.Pro1137Leu Likely pathogenic ★★ same condition
FLT4 p.Ser393Arg Uncertain significance ★★ ⚠ same condition
FLT4 c.2168-1G>A Likely pathogenic ★ same condition
FLT4 p.Arg1041Gly Likely pathogenic ★ same condition
FLT4 p.Gln1020Leu Pathogenic ★ same condition
FLT4 p.Gln1179Ter Pathogenic ★ same condition
FLT4 p.Gly1276Glu Likely pathogenic ★ 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-leu192 (accessed [today's date]).

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