Is F9 p.Arg384Ter (c.1150C>T) pathogenic?

F9 p.Arg384Ter (c.1150C>T) is classified Pathogenic in F9 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-21). Very rare (popmax 0.00175%, afr); Associated with F9-related disorder.

What condition is associated with F9 p.Arg384Ter (c.1150C>T)?

F9 p.Arg384Ter (c.1150C>T) is associated with F9-related disorder, thrombophilia, X-linked, due to factor 9 defect, hemophilia B (ClinVar).

How common is F9 p.Arg384Ter (c.1150C>T) in the general population?

F9 p.Arg384Ter (c.1150C>T) is very rare (popmax 0.00175%, afr) (gnomAD).

F9 p.Arg384Ter

c.1150C>T · rs137852261 · VCV10615

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00175%, afr)

Conditions

F9-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 3.3, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% African / African-American · 1/57,105 alleles

Overall 0.000894% 1/111,885 alleles · very rare

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: F9
Protein: p.Arg384Ter
Coding: c.1150C>T
MANE Select: NM_000133
dbSNP: rs137852261
Type: single nucleotide variant
Location: chrX:139561835 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 384: a UniProt-annotated variant site (in thph8; factor ix padua; higher specific activity than wild-type); an α-helix; a disulfide bond; the peptidase s1 domain

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

Disease context

F9-related disorder

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

Similar variants

F9 p.Arg384Gln Benign ★★★ same residue
F9 p.Arg384Leu Pathogenic ⚠ same residue
F9 p.Arg384Pro Pathogenic same residue
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

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-arg384ter (accessed [today's date]).

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