Is F9 p.Cys128Ter (c.384T>A) pathogenic?

F9 p.Cys128Ter (c.384T>A) is classified Pathogenic/Likely pathogenic in F9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-05). Absent from gnomAD v4.1; Associated with Warfarin sensitivity, X-linked.

What condition is associated with F9 p.Cys128Ter (c.384T>A)?

F9 p.Cys128Ter (c.384T>A) is associated with Warfarin sensitivity, X-linked, thrombophilia, X-linked, due to factor 9 defect, hemophilia B (ClinVar).

How common is F9 p.Cys128Ter (c.384T>A) in the general population?

F9 p.Cys128Ter (c.384T>A) is absent from gnomAD v4.1 (gnomAD).

F9 p.Cys128Ter

c.384T>A · rs780435919 · VCV1438328

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Warfarin sensitivity, X-linked

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	predicted	premature termination codon in exon 4 of 8
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.30	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 3.4	GERP 4.1, phastCons 1
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.Cys128Ter
Coding: c.384T>A
MANE Select: NM_000133
dbSNP: rs780435919
Type: single nucleotide variant
Location: chrX:139541182 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 128: a turn; the egf-like 1; calcium-binding domain; a disulfide bond

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

Disease context

Warfarin sensitivity, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

F9 p.Cys128Arg Likely pathogenic ★ same residue
F9 p.Cys128= Likely benign ★ 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
F9 p.Ala337Thr 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-cys128ter (accessed [today's date]).

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