Is FLT3 p.Phe537Val (c.1609T>G) pathogenic?

FLT3 p.Phe537Val (c.1609T>G) is classified Uncertain significance in FLT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-18). AlphaMissense: likely benign (0.0647); Very rare (popmax 0.00333%, amr).

How common is FLT3 p.Phe537Val (c.1609T>G) in the general population?

FLT3 p.Phe537Val (c.1609T>G) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about FLT3 p.Phe537Val (c.1609T>G)?

AlphaMissense predicts likely benign (score 0.0647) — an in-silico prediction, not a clinical call.

FLT3 p.Phe537Val

c.1609T>G · VCV3516099

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0647 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0647	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -5.98	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 3.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 96 kb · p 0.00044 · regional, not allelic
Overall
CADD	18.63	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 0.00333% Admixed American · 2/60,028 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000342% 5/1,460,608 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,014
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)	0.00017%	589,456

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: FLT3
Protein: p.Phe537Val
Coding: c.1609T>G
MANE Select: NM_004119
Type: single nucleotide variant
Location: chr13:28034396 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.19 · 11 PDB

Full FLT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FLT3 c.1205+56C>T Benign ★★ same type
FLT3 c.1310-3T>C Benign ★★ same type
FLT3 c.1418+75A>G Benign ★★ same type
FLT3 c.1418+81A>G Benign ★★ same type
FLT3 c.1419-15T>C Benign ★★ same type
FLT3 c.1419-36T>A Benign ★★ same type
FLT3 c.1597+8A>G Likely benign ★★ same type
FLT3 c.165+118G>T Benign ★★ 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/flt3-p-phe537val (accessed [today's date]).

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