Is FLT4 p.Val1355Met (c.4063G>A) pathogenic?

FLT4 p.Val1355Met (c.4063G>A) is classified Likely benign in FLT4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-01). AlphaMissense: likely benign (0.0949); Low-frequency (popmax 1.22%, mid).

How common is FLT4 p.Val1355Met (c.4063G>A) in the general population?

FLT4 p.Val1355Met (c.4063G>A) is low-frequency (popmax 1.22%, mid) (gnomAD).

What do computational predictors say about FLT4 p.Val1355Met (c.4063G>A)?

AlphaMissense predicts likely benign (score 0.0949) — an in-silico prediction, not a clinical call.

FLT4 p.Val1355Met

c.4063G>A · rs143739828 · VCV3042470

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0949 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.22%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0949	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -8.61	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 -3.7	GERP -2.9
Regional constraint	o/e 0.95	unconstrained · MANE · 9,843 bp · p 0.36 · regional, not allelic
Overall
CADD	3.719	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 1.22% Middle Eastern · 74/6,062 alleles

Filtering AF 0.997% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.915%

Overall 0.0899% 1,451/1,614,070 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.22%	82
Ashkenazi Jewishnot grpmax-eligible	0.831%	120
African / African-American	0.374%	267
Remaining individualsnot grpmax-eligible	0.192%	521
Admixed American	0.162%	619
South Asian	0.0505%	1,980
European (non-Finnish)	0.0493%	2,028
Finnishnot grpmax-eligible	0.00783%	12,773

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.Val1355Met
Coding: c.4063G>A
MANE Select: NM_182925
dbSNP: rs143739828
Type: single nucleotide variant
Location: chr5:180603221 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 1355: 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.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
FLT4 p.Ala855Thr 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-val1355met (accessed [today's date]).

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