Is FLT3 p.Ala988Pro (c.2962G>C) pathogenic?

FLT3 p.Ala988Pro (c.2962G>C) is classified Benign in FLT3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.069); Low-frequency (popmax 2.96%, afr).

How common is FLT3 p.Ala988Pro (c.2962G>C) in the general population?

FLT3 p.Ala988Pro (c.2962G>C) is low-frequency (popmax 2.96%, afr) (gnomAD).

What do computational predictors say about FLT3 p.Ala988Pro (c.2962G>C)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

FLT3 p.Ala988Pro

c.2962G>C · rs74041526 · VCV134441

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.96%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -5.77	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 0.019	GERP -1.1
Regional constraint	o/e 0.90	unconstrained · MANE · 96 kb · p 0.00044 · regional, not allelic
Overall
CADD	3.709	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 2.96% African / African-American · 2,222/75,006 alleles

Filtering AF 2.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.82%

Overall 0.16% 2,590/1,614,070 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.96%	34
Remaining individualsnot grpmax-eligible	0.234%	428
Middle Eastern	0.182%	550
Admixed American	0.145%	689
South Asian	0.011%	9,107
European (non-Finnish)	0.00966%	10,351

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.Ala988Pro
Coding: c.2962G>C
MANE Select: NM_004119
dbSNP: rs74041526
Type: single nucleotide variant
Location: chr13:28004072 (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-ala988pro (accessed [today's date]).

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