Is FLT4 p.Thr28Ala (c.82A>G) pathogenic?

FLT4 p.Thr28Ala (c.82A>G) is classified Uncertain significance in FLT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-21). AlphaMissense: likely benign (0.1196); Very rare (popmax 0.00334%, amr).

How common is FLT4 p.Thr28Ala (c.82A>G) in the general population?

FLT4 p.Thr28Ala (c.82A>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about FLT4 p.Thr28Ala (c.82A>G)?

AlphaMissense predicts likely benign (score 0.1196) — an in-silico prediction, not a clinical call.

FLT4 p.Thr28Ala

c.82A>G · VCV4527451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1196 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1196	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -4.98	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 6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 19 kb · p 0.1 · regional, not allelic
Overall
CADD	23.4	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 0.00334% Admixed American · 2/59,900 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,609,026 alleles · very rare

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.Thr28Ala
Coding: c.82A>G
MANE Select: NM_182925
Type: single nucleotide variant
Location: chr5:180631755 (GRCh38)
Gene constraint: LOEUF 0.265 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.82 · 2 PDB

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-thr28ala (accessed [today's date]).

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