Is FLT4 p.Phe1027Leu (c.3079T>C) pathogenic?

FLT4 p.Phe1027Leu (c.3079T>C) is classified Uncertain significance in FLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-02). AlphaMissense: likely pathogenic (0.9974); Absent from gnomAD v4.1; Associated with FLT4-related disorder.

What condition is associated with FLT4 p.Phe1027Leu (c.3079T>C)?

FLT4 p.Phe1027Leu (c.3079T>C) is associated with FLT4-related disorder (ClinVar).

How common is FLT4 p.Phe1027Leu (c.3079T>C) in the general population?

FLT4 p.Phe1027Leu (c.3079T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLT4 p.Phe1027Leu (c.3079T>C)?

AlphaMissense predicts likely pathogenic (score 0.9974) — an in-silico prediction, not a clinical call.

FLT4 p.Phe1027Leu

c.3079T>C · rs764532088 · VCV2636467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9974 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FLT4-related disorder

Computational evidence

Protein change
AlphaMissense	0.9974	likely pathogenic · top 2% in FLT4
REVEL	0.927	moderately pathogenic-leaning
SaProt	LLR -14.29	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 15 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Phe1027Leu
Coding: c.3079T>C
MANE Select: NM_182925
dbSNP: rs764532088
Type: single nucleotide variant
Location: chr5:180616917 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 1027: the protein kinase domain; 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.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-phe1027leu (accessed [today's date]).

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