Is FLT3 p.Gln426= (c.1278A>G) pathogenic?

FLT3 p.Gln426= (c.1278A>G) is classified Benign in FLT3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Rare (popmax 0.213%, nfe).

How common is FLT3 p.Gln426= (c.1278A>G) in the general population?

FLT3 p.Gln426= (c.1278A>G) is rare (popmax 0.213%, nfe) (gnomAD).

FLT3 p.Gln426=

c.1278A>G · rs56152292 · VCV769395

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.213%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -2.4, phastCons 0.081
Overall
CADD	6.969	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.213% European (non-Finnish) · 2,499/1,174,212 alleles

Filtering AF 0.206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.203%

Overall 0.223% 3,584/1,607,616 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.22%	82
European (non-Finnish)grpmax	0.213%	470
Remaining individualsnot grpmax-eligible	0.161%	623
Ashkenazi Jewishnot grpmax-eligible	0.145%	688
South Asian	0.106%	947
Middle Eastern	0.0669%	1,495
Admixed American	0.06%	1,667
African / African-American	0.032%	3,122

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln426=
Coding: c.1278A>G
MANE Select: NM_004119
dbSNP: rs56152292
Type: single nucleotide variant
Location: chr13:28037216 (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-gln426 (accessed [today's date]).

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