Is FLT1 p.Val587Ile (c.1759G>A) pathogenic?

FLT1 p.Val587Ile (c.1759G>A) is classified Likely benign in FLT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely benign (0.0547); Very rare (popmax 0.00267%, afr).

How common is FLT1 p.Val587Ile (c.1759G>A) in the general population?

FLT1 p.Val587Ile (c.1759G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about FLT1 p.Val587Ile (c.1759G>A)?

AlphaMissense predicts likely benign (score 0.0547) — an in-silico prediction, not a clinical call.

FLT1 p.Val587Ile

c.1759G>A · VCV3516076

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0547 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0547	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -5.39	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 -2.6	GERP -5.1
Regional constraint	o/e 0.79	unconstrained · MANE · 173 kb · p 9.5e-14 · regional, not allelic
Overall
CADD	0.024	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 0.00267% African / African-American · 2/74,918 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000929% 15/1,614,040 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,459
Admixed American	0.00167%	59,998
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000932%	107,275

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: FLT1
Protein: p.Val587Ile
Coding: c.1759G>A
MANE Select: NM_002019
Type: single nucleotide variant
Location: chr13:28390006 (GRCh38)
Gene constraint: LOEUF 0.379 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.86 · 12 PDB
Residue 587: the ig-like c2-type 6 domain; a disulfide bond

Full FLT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FLT1 p.Asp6Asn Benign ★★ same type
FLT1 p.Cys107= Likely benign ★★ same type
FLT1 p.Ile548Met Likely benign ★★ ⚠ same type
FLT1 p.Leu492= Benign ★★ same type
FLT1 p.Met938Val Likely benign ★★ same type
FLT1 p.Pro1068= Benign ★★ same type
FLT1 p.Pro1201Leu Likely benign ★★ same type
FLT1 p.Thr260= 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/flt1-p-val587ile (accessed [today's date]).

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