Is FLT1 p.Phe88Leu (c.262T>C) pathogenic?

FLT1 p.Phe88Leu (c.262T>C) is classified Uncertain significance in FLT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely pathogenic (0.8305); Absent from gnomAD v4.1.

How common is FLT1 p.Phe88Leu (c.262T>C) in the general population?

FLT1 p.Phe88Leu (c.262T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLT1 p.Phe88Leu (c.262T>C)?

AlphaMissense predicts likely pathogenic (score 0.8305) — an in-silico prediction, not a clinical call.

FLT1 p.Phe88Leu

c.262T>C · rs2502547565 · VCV2643708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8305 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8305	likely pathogenic
REVEL	0.305	indeterminate
SaProt	LLR -5.07	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 173 kb · p 9.5e-14 · regional, not allelic
Overall
CADD	23.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLT1
Protein: p.Phe88Leu
Coding: c.262T>C
MANE Select: NM_002019
dbSNP: rs2502547565
Type: single nucleotide variant
Location: chr13:28467029 (GRCh38)
Gene constraint: LOEUF 0.379 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.86 · 12 PDB
Residue 88: a disulfide bond; the ig-like c2-type 1 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-phe88leu (accessed [today's date]).

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