Is F9 p.Ile390Phe (c.1168A>T) pathogenic?

F9 p.Ile390Phe (c.1168A>T) is classified Likely pathogenic in F9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). AlphaMissense: ambiguous (0.4044); Absent from gnomAD v4.1; Associated with F9-related disorder.

What condition is associated with F9 p.Ile390Phe (c.1168A>T)?

F9 p.Ile390Phe (c.1168A>T) is associated with F9-related disorder (ClinVar).

How common is F9 p.Ile390Phe (c.1168A>T) in the general population?

F9 p.Ile390Phe (c.1168A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F9 p.Ile390Phe (c.1168A>T)?

AlphaMissense predicts ambiguous (score 0.4044) — an in-silico prediction, not a clinical call.

F9 p.Ile390Phe

c.1168A>T · rs1287011273 · VCV2632738

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4044 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

F9-related disorder

Computational evidence

Protein change
AlphaMissense	0.4044	ambiguous
REVEL	0.839	moderately pathogenic-leaning
SaProt	LLR -9.61	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 3.9, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 25 kb · p 2.3e-14 · regional, not allelic
Overall
CADD	24.0	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: F9
Protein: p.Ile390Phe
Coding: c.1168A>T
MANE Select: NM_000133
dbSNP: rs1287011273
Type: single nucleotide variant
Location: chrX:139561853 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 390: a UniProt-annotated variant site (in hemb; severe); the peptidase s1 domain

Full F9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

F9-related disorder

Similar variants

F9 p.Ile390= Likely benign ★ same residue
F9 p.Arg226Trp Pathogenic/Likely pathogenic ★★ same condition
F9 p.Arg379Gln Pathogenic ★★ ⚠ same condition
F9 p.Arg384Ter Pathogenic ★★ same condition
F9 p.Arg43Leu Pathogenic ★★ same condition
F9 p.Cys28Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
F9 p.Gln241Arg Likely pathogenic ★★ same condition
F9 c.277+1G>T Pathogenic ★ same condition

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/f9-p-ile390phe (accessed [today's date]).

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