Is F8 p.Phe2294fs (c.6876_6877del) pathogenic?

F8 p.Phe2294fs (c.68766877del) is classified Pathogenic in F8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-01). Absent from gnomAD; Associated with hemophilia A.

What condition is associated with F8 p.Phe2294fs (c.6876_6877del)?

F8 p.Phe2294fs (c.6876_6877del) is associated with hemophilia A (ClinVar).

How common is F8 p.Phe2294fs (c.6876_6877del) in the general population?

F8 p.Phe2294fs (c.6876_6877del) is absent from gnomAD (gnomAD).

How is Hemophilia A inherited?

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

F8 p.Phe2294fs

c.6876_6877del · rs1356674990 · VCV973809

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hemophilia A

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (25 of 26, 23 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.3	GERP -0.12, phastCons 1

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.Phe2294fs
Coding: c.6876_6877del
MANE Select: NM_000132
dbSNP: rs1356674990
Type: Microsatellite
Location: chrX:154860455 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 2294: the f5/8 type c 2 domain; a disulfide bond

Full F8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Hemophilia A (Orphanet):

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

Similar variants

F8 p.Thr252fs Pathogenic ★★ same condition
F8 p.His2156fs Pathogenic ★ same condition
F8 p.Leu69fs Pathogenic ★ same condition
F8 p.Lys1443fs Pathogenic ★ same condition
F8 p.Ser806fs Pathogenic ★ same condition
F8 p.Tyr1834fs Pathogenic ★ same condition
F8 p.Tyr65fs Likely pathogenic ★ same condition
F8 p.Phe672del Uncertain significance ★ 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-phe2294fs (accessed [today's date]).

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