Is FLT4 p.Lys858Arg (c.2573A>G) pathogenic?

FLT4 p.Lys858Arg (c.2573A>G) is classified Uncertain significance in FLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.1139); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with FLT4 p.Lys858Arg (c.2573A>G)?

FLT4 p.Lys858Arg (c.2573A>G) is associated with Inborn genetic diseases (ClinVar).

How common is FLT4 p.Lys858Arg (c.2573A>G) in the general population?

FLT4 p.Lys858Arg (c.2573A>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about FLT4 p.Lys858Arg (c.2573A>G)?

AlphaMissense predicts likely benign (score 0.1139) — an in-silico prediction, not a clinical call.

FLT4 p.Lys858Arg

c.2573A>G · rs764609077 · VCV3095749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1139 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1139	likely benign
REVEL	0.513	indeterminate
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.26	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 15 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00333% Admixed American · 2/60,028 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000137% 2/1,460,182 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.Lys858Arg
Coding: c.2573A>G
MANE Select: NM_182925
dbSNP: rs764609077
Type: single nucleotide variant
Location: chr5:180619739 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 858: the protein kinase domain; a binding site; 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-lys858arg (accessed [today's date]).

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