Is F8 p.Ser1439fs (c.4313dup) pathogenic?

F8 p.Ser1439fs (c.4313dup) is classified Likely pathogenic in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-01). Absent from gnomAD; Associated with hemophilia B.

What condition is associated with F8 p.Ser1439fs (c.4313dup)?

F8 p.Ser1439fs (c.4313dup) is associated with hemophilia B (ClinVar).

How common is F8 p.Ser1439fs (c.4313dup) in the general population?

F8 p.Ser1439fs (c.4313dup) is absent from gnomAD (gnomAD).

How is Hemophilia B inherited?

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

F8 p.Ser1439fs

c.4313dup · rs1603433756 · VCV627064

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hemophilia B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 14 of 26
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.14	GERP -3.4, phastCons 0.079

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: F8
Protein: p.Ser1439fs
Coding: c.4313dup
MANE Select: NM_000132
dbSNP: rs1603433756
Type: Duplication
Location: chrX:154929476 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 1439: the 'b' region

Full F8 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

For Hemophilia B (Orphanet):

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

Similar variants

F8 p.Asn358fs Likely pathogenic ★ same condition
F8 p.Arg602Ter Pathogenic ★★★ same condition
F8 p.Arg612Cys Pathogenic ★★★ ⚠ same condition
F8 p.Asn1739= Likely pathogenic ★★★ same condition
F8 p.Ile1213fs Pathogenic ★★★ same condition
F8 p.Leu327Val Pathogenic ★★★ ⚠ same condition
F8 p.Trp2248Cys Pathogenic ★★★ same condition
F8 p.Tyr365Cys 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/f8-p-ser1439fs (accessed [today's date]).

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