Is FLT4 p.Ala1022Val (c.3065C>T) pathogenic?

FLT4 p.Ala1022Val (c.3065C>T) is classified Uncertain significance in FLT4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-05-07). AlphaMissense: likely pathogenic (0.8986); Absent from gnomAD v4.1; Associated with colon carcinoma.

What condition is associated with FLT4 p.Ala1022Val (c.3065C>T)?

FLT4 p.Ala1022Val (c.3065C>T) is associated with colon carcinoma (ClinVar).

How common is FLT4 p.Ala1022Val (c.3065C>T) in the general population?

FLT4 p.Ala1022Val (c.3065C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLT4 p.Ala1022Val (c.3065C>T)?

AlphaMissense predicts likely pathogenic (score 0.8986) — an in-silico prediction, not a clinical call.

FLT4 p.Ala1022Val

c.3065C>T · rs56364366 · VCV204355

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8986 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

colon carcinoma

Computational evidence

Protein change
AlphaMissense	0.8986	likely pathogenic
REVEL	0.856	moderately pathogenic-leaning
SaProt	LLR -13.65	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 15 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLT4
Protein: p.Ala1022Val
Coding: c.3065C>T
MANE Select: NM_182925
dbSNP: rs56364366
Type: single nucleotide variant
Location: chr5:180616931 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB
Residue 1022: the protein kinase domain; a UniProt-annotated variant site (in chtd7)

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

Disease context

colon carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLT4 p.Ala1022fs Uncertain significance same residue
FLT4 p.Ala702Ser Uncertain significance ★★ ⚠ same condition
FLT4 p.Pro641Ser Benign/Likely benign ★★ same condition
FLT4 c.2407-7C>T Uncertain significance same condition
FLT4 c.2542+12A>G Uncertain significance same condition
FLT4 c.3002-9A>C Uncertain significance same condition
FLT4 p.Asp834Glu Uncertain significance ⚠ same condition
FLT4 p.Gly811= 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-ala1022val (accessed [today's date]).

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