Is FLT4 p.Glu350Val (c.1049A>T) pathogenic?

FLT4 p.Glu350Val (c.1049A>T) is classified Benign in FLT4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-09-11). AlphaMissense: likely benign (0.1872); Low-frequency (popmax 1.41%, afr).

How common is FLT4 p.Glu350Val (c.1049A>T) in the general population?

FLT4 p.Glu350Val (c.1049A>T) is low-frequency (popmax 1.41%, afr) (gnomAD).

What do computational predictors say about FLT4 p.Glu350Val (c.1049A>T)?

AlphaMissense predicts likely benign (score 0.1872) — an in-silico prediction, not a clinical call.

FLT4 p.Glu350Val

c.1049A>T · rs111916034 · VCV263015

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1872 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.41%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1872	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -6.17	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 5.1	GERP 0.4, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 15 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	22.7	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 1.41% African / African-American · 1,057/75,022 alleles

Filtering AF 1.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.31%

Overall 0.0766% 1,236/1,612,714 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.41%	71
Remaining individualsnot grpmax-eligible	0.128%	781
Admixed American	0.0983%	1,017
Middle Eastern	0.033%	3,030
South Asian	0.00769%	13,012
European (non-Finnish)	0.00263%	38,063

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.Glu350Val
Coding: c.1049A>T
MANE Select: NM_182925
dbSNP: rs111916034
Type: single nucleotide variant
Location: chr5:180628936 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 350: a β-strand; a UniProt-annotated variant site (in chtd7); the ig-like c2-type 4 domain

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

Similar variants

FLT4 p.Glu350Lys Uncertain significance ★ 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-glu350val (accessed [today's date]).

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