Is FLT4 p.Ile796Thr (c.2387T>C) pathogenic?

FLT4 p.Ile796Thr (c.2387T>C) is classified Uncertain significance in FLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely pathogenic (0.6311); Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FLT4 p.Ile796Thr (c.2387T>C)?

FLT4 p.Ile796Thr (c.2387T>C) is associated with Inborn genetic diseases (ClinVar).

How common is FLT4 p.Ile796Thr (c.2387T>C) in the general population?

FLT4 p.Ile796Thr (c.2387T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about FLT4 p.Ile796Thr (c.2387T>C)?

AlphaMissense predicts likely pathogenic (score 0.6311) — an in-silico prediction, not a clinical call.

FLT4 p.Ile796Thr

c.2387T>C · rs2480904159 · VCV3095747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6311 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6311	likely pathogenic
REVEL	0.746	pathogenic-leaning
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
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	26.8	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

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,252 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,460,390 alleles · very rare

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.Ile796Thr
Coding: c.2387T>C
MANE Select: NM_182925
dbSNP: rs2480904159
Type: single nucleotide variant
Location: chr5:180620628 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 796: a UniProt-annotated variant site (in chtd7)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLT4 p.Gly1131Ser Pathogenic/Likely pathogenic ★★ same condition
FLT4 p.Ala702Ser Uncertain significance ★★ ⚠ same condition
FLT4 p.Arg1189His Uncertain significance ★★ ⚠ same condition
FLT4 p.Glu207Lys Uncertain significance ★★ ⚠ same condition
FLT4 p.Glu365Lys Uncertain significance ★★ ⚠ same condition
FLT4 p.Gly4Ala Uncertain significance ★★ ⚠ same condition
FLT4 p.Met1260Leu Uncertain significance ★★ ⚠ same condition
FLT4 p.Pro922Leu 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-ile796thr (accessed [today's date]).

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