Is FLT3 p.Ser356Asn (c.1067G>A) pathogenic?

FLT3 p.Ser356Asn (c.1067G>A) is classified Uncertain significance in FLT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely benign (0.0671); Very rare (popmax 0.00167%, amr).

How common is FLT3 p.Ser356Asn (c.1067G>A) in the general population?

FLT3 p.Ser356Asn (c.1067G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about FLT3 p.Ser356Asn (c.1067G>A)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

FLT3 p.Ser356Asn

c.1067G>A · rs776892297 · VCV2307337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -6.65	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 -0.63	GERP -3.8
Regional constraint	o/e 0.90	unconstrained · MANE · 96 kb · p 0.00044 · regional, not allelic
Overall
CADD	6.979	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 0.00167% Admixed American · 1/59,970 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000274% 4/1,457,280 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,970
South Asian	0.0011%	90,804
European (non-Finnish)	0.00017%	588,069

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.Ser356Asn
Coding: c.1067G>A
MANE Select: NM_004119
dbSNP: rs776892297
Type: single nucleotide variant
Location: chr13:28048413 (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-ser356asn (accessed [today's date]).

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