Is FLT4 p.Asp1274Val (c.3821A>T) pathogenic?

FLT4 p.Asp1274Val (c.3821A>T) is classified Likely pathogenic in FLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-10-19). AlphaMissense: likely pathogenic (0.9082); Absent from gnomAD v4.1; Associated with lymphatic malformation 1.

What condition is associated with FLT4 p.Asp1274Val (c.3821A>T)?

FLT4 p.Asp1274Val (c.3821A>T) is associated with lymphatic malformation 1 (ClinVar).

How common is FLT4 p.Asp1274Val (c.3821A>T) in the general population?

FLT4 p.Asp1274Val (c.3821A>T) is absent from gnomAD v4.1 (gnomAD).

How is Milroy disease inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FLT4 p.Asp1274Val (c.3821A>T)?

AlphaMissense predicts likely pathogenic (score 0.9082) — an in-silico prediction, not a clinical call.

FLT4 p.Asp1274Val

c.3821A>T · rs1761973773 · VCV1030389

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9082 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lymphatic malformation 1

Computational evidence

Protein change
AlphaMissense	0.9082	likely pathogenic ✓ concordant with ClinVar
REVEL	0.798	moderately pathogenic-leaning
SaProt	LLR -10.56	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.99, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 9,843 bp · p 0.36 · regional, not allelic
Overall
CADD	28.1	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: FLT4
Protein: p.Asp1274Val
Coding: c.3821A>T
MANE Select: NM_182925
dbSNP: rs1761973773
Type: single nucleotide variant
Location: chr5:180609040 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 1274: a UniProt-annotated variant site (in chtd7)

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

Disease context

lymphatic malformation 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Milroy disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Antenatal, Infancy, Neonatal

Similar variants

FLT4 p.Asp1274His Uncertain significance ★ ⚠ same residue
FLT4 p.Asp1274Asn Uncertain significance ★★ ⚠ same residue
FLT4 p.Asp1274Gly Uncertain significance ★ ⚠ same residue
FLT4 p.Arg1041Gln Pathogenic/Likely pathogenic ★★ same condition
FLT4 p.Arg1041Trp Pathogenic/Likely pathogenic ★★ same condition
FLT4 p.Gly857Arg Pathogenic ★★ same condition
FLT4 p.Pro1137Leu Likely pathogenic ★★ same condition
FLT4 p.Ala702Ser 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-asp1274val (accessed [today's date]).

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