Is F9 p.Arg379Ter (c.1135C>T) pathogenic?

F9 p.Arg379Ter (c.1135C>T) is classified Pathogenic in F9 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-07-22). Absent from gnomAD v4.1; Associated with thrombophilia, X-linked, due to factor 9 defect.

What condition is associated with F9 p.Arg379Ter (c.1135C>T)?

F9 p.Arg379Ter (c.1135C>T) is associated with thrombophilia, X-linked, due to factor 9 defect, hemophilia B (ClinVar).

How common is F9 p.Arg379Ter (c.1135C>T) in the general population?

F9 p.Arg379Ter (c.1135C>T) is absent from gnomAD v4.1 (gnomAD).

F9 p.Arg379Ter

c.1135C>T · rs137852258 · VCV10612

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

thrombophilia, X-linked, due to factor 9 defect

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 0.43	GERP 3.3, phastCons 0.99
Overall
CADD	36.0	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

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.Arg379Ter
Coding: c.1135C>T
MANE Select: NM_000133
dbSNP: rs137852258
Type: single nucleotide variant
Location: chrX:139561820 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 379: a UniProt-annotated variant site (in hemb; moderate); a UniProt-annotated variant site (in hemb; severe; iceland-1, london and sesimbra); an α-helix; the peptidase s1 domain

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

Disease context

thrombophilia, X-linked, due to factor 9 defect — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hemophilia B

Similar variants

F9 p.Arg379Gln Pathogenic ★★ ⚠ same residue
F9 p.Arg379Leu Pathogenic ★ ⚠ same residue
F9 p.Arg379= Uncertain significance 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-arg379ter (accessed [today's date]).

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