Is FLT4 p.Glu570Asp (c.1710G>C) pathogenic?

FLT4 p.Glu570Asp (c.1710G>C) is classified Uncertain significance in FLT4 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-04-03). AlphaMissense: likely pathogenic (0.7187); Very rare (popmax 8.47e-05%, nfe).

How common is FLT4 p.Glu570Asp (c.1710G>C) in the general population?

FLT4 p.Glu570Asp (c.1710G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about FLT4 p.Glu570Asp (c.1710G>C)?

AlphaMissense predicts likely pathogenic (score 0.7187) — an in-silico prediction, not a clinical call.

FLT4 p.Glu570Asp

c.1710G>C · rs758989887 · VCV3046561

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7187 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7187	likely pathogenic
REVEL	0.143	moderately benign-leaning
SaProt	LLR -9.97	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.004	GERP -2.6, phastCons 0.82
Regional constraint	o/e 0.86	unconstrained · MANE · 15 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	21.0	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 8.47e-05% European (non-Finnish) · 1/1,179,970 alleles

Overall 6.84e-05% 1/1,461,112 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.Glu570Asp
Coding: c.1710G>C
MANE Select: NM_182925
dbSNP: rs758989887
Type: single nucleotide variant
Location: chr5:180621852 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 570: the ig-like c2-type 6 domain; a UniProt-annotated variant site (in chtd7)

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

Similar variants

FLT4 p.Glu570fs Pathogenic ★ same residue
FLT4 p.Arg1041Gln Pathogenic/Likely pathogenic ★★ same type
FLT4 p.Arg1041Trp Pathogenic/Likely pathogenic ★★ same type
FLT4 p.Arg318Ter Pathogenic/Likely pathogenic ★★ same type
FLT4 p.Gly1131Ser Pathogenic/Likely pathogenic ★★ same type
FLT4 p.Gly857Arg Pathogenic ★★ same type
FLT4 p.Pro1137Leu Likely pathogenic ★★ same type
FLT4 p.Ala702Ser Uncertain significance ★★ ⚠ same type

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-glu570asp (accessed [today's date]).

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