Is FLT1 p.Ile552Val (c.1654A>G) pathogenic?

FLT1 p.Ile552Val (c.1654A>G) is classified Likely benign in FLT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.0556); Very rare (popmax 0.00404%, afr).

How common is FLT1 p.Ile552Val (c.1654A>G) in the general population?

FLT1 p.Ile552Val (c.1654A>G) is very rare (popmax 0.00404%, afr) (gnomAD).

What do computational predictors say about FLT1 p.Ile552Val (c.1654A>G)?

AlphaMissense predicts likely benign (score 0.0556) — an in-silico prediction, not a clinical call.

FLT1 p.Ile552Val

c.1654A>G · VCV4258372

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0556 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00404%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0556	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -3.97	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 -3.5	GERP -4.8
Regional constraint	o/e 0.79	unconstrained · MANE · 173 kb · p 9.5e-14 · regional, not allelic
Overall
CADD	0.152	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 0.00404% African / African-American · 3/74,320 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000497%

Overall 0.000381% 6/1,575,288 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00404%	24,773
South Asian	0.00332%	30,102

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.Ile552Val
Coding: c.1654A>G
MANE Select: NM_002019
Type: single nucleotide variant
Location: chr13:28396966 (GRCh38)
Gene constraint: LOEUF 0.379 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.86 · 12 PDB
Residue 552: the ig-like c2-type 5 domain

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-ile552val (accessed [today's date]).

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