Is FLT3 p.Asp7Gly (c.20A>G) pathogenic?

FLT3 p.Asp7Gly (c.20A>G) is classified Benign in FLT3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-09). AlphaMissense: likely benign (0.0507); Common (popmax 59.9%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about FLT3 p.Asp7Gly (c.20A>G)?

AlphaMissense predicts likely benign (score 0.0507) — an in-silico prediction, not a clinical call.

FLT3 p.Asp7Gly

Q: How common is FLT3 p.Asp7Gly (c.20A>G) in the general population?

FLT3 p.Asp7Gly (c.20A>G) is common (popmax 59.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.20A>G · rs12872889 · VCV1251597

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0507 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 59.9%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0507	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -4.04	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 -0.22	GERP -2.7
Regional constraint	o/e 0.90	unconstrained · MANE · 96 kb · p 0.00044 · regional, not allelic
Overall
CADD	15.62	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 59.9% African / African-American · 38,078/63,560 alleles

Filtering AF 59.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 59.2%

Overall 26% 315,534/1,215,602 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	59.9%	2
East Asian	33.7%	3
Finnishnot grpmax-eligible	29.1%	3
Middle Eastern	27.9%	4
South Asian	26.9%	4
Remaining individualsnot grpmax-eligible	26.8%	4
European (non-Finnish)	23.6%	4
Amishnot grpmax-eligible	20.8%	5
Admixed American	20.7%	5
Ashkenazi Jewishnot grpmax-eligible	19.2%	5

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.Asp7Gly
Coding: c.20A>G
MANE Select: NM_004119
dbSNP: rs12872889
Type: single nucleotide variant
Location: chr13:28100491 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.19 · 11 PDB
Residue 7: a UniProt-annotated variant site (in)

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-asp7gly (accessed [today's date]).

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