Is FLT3 p.Thr475Pro (c.1423A>C) pathogenic?

FLT3 p.Thr475Pro (c.1423A>C) is classified Likely benign in FLT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-19). AlphaMissense: likely benign (0.1105); Rare (popmax 0.221%, eas).

How common is FLT3 p.Thr475Pro (c.1423A>C) in the general population?

FLT3 p.Thr475Pro (c.1423A>C) is rare (popmax 0.221%, eas) (gnomAD).

What do computational predictors say about FLT3 p.Thr475Pro (c.1423A>C)?

AlphaMissense predicts likely benign (score 0.1105) — an in-silico prediction, not a clinical call.

FLT3 p.Thr475Pro

c.1423A>C · rs149057582 · VCV773836

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1105 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.221%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1105	likely benign
REVEL	0.426	indeterminate
SaProt	LLR -10.58	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.92, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 96 kb · p 0.00044 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 0.221% East Asian · 99/44,836 alleles

Filtering AF 0.186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.172%

Overall 0.00681% 109/1,601,302 alleles · rare exomes 79/1,449,232 · genomes 30/152,070 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.221%	453
Remaining individualsnot grpmax-eligible	0.00968%	10,326
Ashkenazi Jewishnot grpmax-eligible	0.00344%	29,042
European (non-Finnish)	0.000255%	392,334

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.Thr475Pro
Coding: c.1423A>C
MANE Select: NM_004119
dbSNP: rs149057582
Type: single nucleotide variant
Location: chr13:28035669 (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-thr475pro (accessed [today's date]).

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