Is F8 p.Phe672del (c.2009TCT[2]) pathogenic?

F8 p.Phe672del (c.2009TCT[2]) is classified Uncertain significance in F8 (ClinVar, Single submitter, 2 submitters). Very rare (popmax 0.000336%, nfe); Associated with hemophilia A.

What condition is associated with F8 p.Phe672del (c.2009TCT[2])?

F8 p.Phe672del (c.2009TCT[2]) is associated with hemophilia A (ClinVar).

How common is F8 p.Phe672del (c.2009TCT[2]) in the general population?

F8 p.Phe672del (c.2009TCT[2]) is very rare (popmax 0.000336%, nfe) (gnomAD).

How is Hemophilia A inherited?

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

F8 p.Phe672del

c.2009TCT[2] · rs1476178386 · VCV10243

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000336%, nfe)

Conditions

hemophilia A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000336% European (non-Finnish) · 3/893,498 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000274% 3/1,095,949 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: F8
Protein: p.Phe672del
Coding: c.2009TCT[2]
MANE Select: NM_000132
dbSNP: rs1476178386
Type: Microsatellite
Location: chrX:154947794 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 672: the plastocyanin-like 4 domain; a disulfide bond; a β-strand; the f5/8 type a 2 domain

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.Phe2294fs 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-phe672del (accessed [today's date]).

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