Is FLT4 p.Ala360Val (c.1079C>T) pathogenic?

FLT4 p.Ala360Val (c.1079C>T) is classified Uncertain significance in FLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-12-08). AlphaMissense: likely pathogenic (0.9327); Very rare (popmax 0.00133%, afr).

How common is FLT4 p.Ala360Val (c.1079C>T) in the general population?

FLT4 p.Ala360Val (c.1079C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about FLT4 p.Ala360Val (c.1079C>T)?

AlphaMissense predicts likely pathogenic (score 0.9327) — an in-silico prediction, not a clinical call.

FLT4 p.Ala360Val

c.1079C>T · rs1057518359 · VCV373341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9327 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9327	likely pathogenic
REVEL	0.677	pathogenic-leaning
SaProt	LLR -9.49	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 15 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	26.3	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 0.00133% African / African-American · 1/74,912 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,611,842 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0016%	62,460
African / African-Americangrpmax	0.00133%	74,912
European (non-Finnish)	0.00017%	589,765

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala360Val
Coding: c.1079C>T
MANE Select: NM_182925
dbSNP: rs1057518359
Type: single nucleotide variant
Location: chr5:180628906 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 360: 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.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-ala360val (accessed [today's date]).

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