Is FLT3 p.Lys709Thr (c.2126A>C) pathogenic?

FLT3 p.Lys709Thr (c.2126A>C) is classified Uncertain significance in FLT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-29). AlphaMissense: likely benign (0.1359); Absent from gnomAD v4.1.

How common is FLT3 p.Lys709Thr (c.2126A>C) in the general population?

FLT3 p.Lys709Thr (c.2126A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLT3 p.Lys709Thr (c.2126A>C)?

AlphaMissense predicts likely benign (score 0.1359) — an in-silico prediction, not a clinical call.

FLT3 p.Lys709Thr

c.2126A>C · rs2500451724 · VCV2231893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1359 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1359	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 96 kb · p 0.00044 · regional, not allelic
Overall
CADD	23.5	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

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: FLT3
Protein: p.Lys709Thr
Coding: c.2126A>C
MANE Select: NM_004119
dbSNP: rs2500451724
Type: single nucleotide variant
Location: chr13:28027169 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.19 · 11 PDB
Residue 709: the protein kinase domain

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-lys709thr (accessed [today's date]).

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