Is F9 p.Ile334= (c.1002T>A) pathogenic?

F9 p.Ile334= (c.1002T>A) is classified Likely benign in F9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-08). Absent from gnomAD v4.1; Associated with hemophilia B.

What condition is associated with F9 p.Ile334= (c.1002T>A)?

F9 p.Ile334= (c.1002T>A) is associated with hemophilia B, thrombophilia, X-linked, due to factor 9 defect (ClinVar).

How common is F9 p.Ile334= (c.1002T>A) in the general population?

F9 p.Ile334= (c.1002T>A) is absent from gnomAD v4.1 (gnomAD).

How is Hemophilia B inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

F9 p.Ile334=

c.1002T>A · rs2520844611 · VCV2949681

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hemophilia B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.23, phastCons 1
Overall
CADD	8.69	PHRED · no single calibrated threshold — expert panels disagree

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.Ile334=
Coding: c.1002T>A
MANE Select: NM_000133
dbSNP: rs2520844611
Type: single nucleotide variant
Location: chrX:139561687 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 334: a disulfide bond; the peptidase s1 domain

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

Disease context

hemophilia B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: thrombophilia, X-linked, due to factor 9 defect

For Hemophilia B (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

F9 c.520+13A>G Pathogenic ★★★ same condition
F9 c.88+1G>A Pathogenic ★★★ same condition
F9 c.88+5G>T Likely pathogenic ★★★ same condition
F9 p.Ala279Thr Pathogenic ★★★ ⚠ same condition
F9 p.Ala337Pro Likely pathogenic ★★★ same condition
F9 p.Ala337Thr Pathogenic ★★★ ⚠ same condition
F9 p.Ala337Val Pathogenic ★★★ ⚠ same condition
F9 p.Arg191His 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-ile334 (accessed [today's date]).

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