Is FLT4 p.Ala702Ser (c.2104G>T) pathogenic?

FLT4 p.Ala702Ser (c.2104G>T) is classified Uncertain significance in FLT4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-08). AlphaMissense: likely benign (0.0754); Ultra-rare (popmax 0.0183%, amr); Associated with Inborn genetic diseases.

What condition is associated with FLT4 p.Ala702Ser (c.2104G>T)?

FLT4 p.Ala702Ser (c.2104G>T) is associated with Inborn genetic diseases, colon carcinoma, lymphatic malformation 1 (ClinVar).

How common is FLT4 p.Ala702Ser (c.2104G>T) in the general population?

FLT4 p.Ala702Ser (c.2104G>T) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about FLT4 p.Ala702Ser (c.2104G>T)?

AlphaMissense predicts likely benign (score 0.0754) — an in-silico prediction, not a clinical call.

FLT4 p.Ala702Ser

c.2104G>T · rs746659265 · VCV802188

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0754 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0754	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -5.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 15 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	22.5	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 0.0183% Admixed American · 11/60,000 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00167% 27/1,612,728 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,455
Remaining individualsnot grpmax-eligible	0.0144%	6,941
European (non-Finnish)	0.000593%	168,572

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.Ala702Ser
Coding: c.2104G>T
MANE Select: NM_182925
dbSNP: rs746659265
Type: single nucleotide variant
Location: chr5:180621169 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 702: the ig-like c2-type 7 domain; a disulfide bond; 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

Also linked: colon carcinoma lymphatic malformation 1

Similar variants

FLT4 p.Ala702Gly Uncertain significance ★ ⚠ same residue
FLT4 p.Arg1041Gln Pathogenic/Likely pathogenic ★★ same condition
FLT4 p.Arg1041Trp Pathogenic/Likely pathogenic ★★ same condition
FLT4 p.Gly1131Ser Pathogenic/Likely pathogenic ★★ same condition
FLT4 p.Gly857Arg Pathogenic ★★ same condition
FLT4 p.Pro1137Leu Likely pathogenic ★★ same condition
FLT4 p.Ala855Thr Uncertain significance ★★ ⚠ same condition
FLT4 p.Arg1060Gln 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-ala702ser (accessed [today's date]).

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