Is FLT3 p.Asp835His (c.2503G>C) pathogenic?

FLT3 p.Asp835His (c.2503G>C) is classified Pathogenic in FLT3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2001-06-01). AlphaMissense: likely pathogenic (0.9725); Absent from gnomAD v4.1; Associated with acute myeloid leukemia.

What condition is associated with FLT3 p.Asp835His (c.2503G>C)?

FLT3 p.Asp835His (c.2503G>C) is associated with acute myeloid leukemia (ClinVar).

How common is FLT3 p.Asp835His (c.2503G>C) in the general population?

FLT3 p.Asp835His (c.2503G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLT3 p.Asp835His (c.2503G>C)?

AlphaMissense predicts likely pathogenic (score 0.9725) — an in-silico prediction, not a clinical call.

FLT3 p.Asp835His

c.2503G>C · rs121913488 · VCV16273

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9725 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

acute myeloid leukemia

Computational evidence

Protein change
AlphaMissense	0.9725	likely pathogenic ✓ concordant with ClinVar · top 8% in FLT3
REVEL	0.878	moderately pathogenic-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 96 kb · p 0.00044 · regional, not allelic
Overall
CADD	29.4	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

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

Cancer therapy — CIViC

Disease	Therapies	Level	Significance
Acute Myeloid Leukemia	Ponatinib,Quizartinib	D	Resistance
Acute Myeloid Leukemia	SU5614	D	Resistance
Acute Myeloid Leukemia	Quizartinib,Sorafenib	B	Resistance
Acute Myeloid Leukemia	Sorafenib	B	Resistance
Acute Myeloid Leukemia	Midostaurin,Chemotherapy	A	Sensitivity/Response
Acute Myeloid Leukemia	Sunitinib	C	Sensitivity/Response
Acute Myeloid Leukemia	Sunitinib	C	Sensitivity/Response
Acute Myeloid Leukemia	Sunitinib	D	Sensitivity/Response

Variant & gene context

Gene: FLT3
Protein: p.Asp835His
Coding: c.2503G>C
MANE Select: NM_004119
dbSNP: rs121913488
Type: single nucleotide variant
Location: chr13:28018505 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.19 · 11 PDB
Residue 835: a UniProt-annotated variant site (in acute lymphoblastic leukemia patients and acute myelogenous leukemia patients; somatic mutation; constitutively activated); a UniProt-annotated variant site (in acute lymphoblastic leukemia patients and in acute myelogenous leukemia patients; somatic mutation; constitutively activated); the protein kinase domain

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

Disease context

acute myeloid leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLT3 p.Asp835Asn Pathogenic ⚠ same residue
FLT3 p.Asp835Glu Pathogenic ⚠ same residue
FLT3 p.Asp835Tyr Pathogenic same residue
FLT3 p.Asp835Val Pathogenic same residue
FLT3 p.Asp835del Pathogenic same residue
FLT3 p.Arg845Gly Likely pathogenic ★ same condition
FLT3 p.Tyr572Cys Likely pathogenic ★ ⚠ same condition
FLT3 p.Ser840_Asn841insGlySer Pathogenic 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/flt3-p-asp835his (accessed [today's date]).

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