Is F8 p.Arg391= (c.1173C>T) pathogenic?

F8 p.Arg391= (c.1173C>T) is classified Uncertain significance in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-28). Very rare (popmax 0.000248%); Associated with hemophilia A.

What condition is associated with F8 p.Arg391= (c.1173C>T)?

F8 p.Arg391= (c.1173C>T) is associated with hemophilia A (ClinVar).

How common is F8 p.Arg391= (c.1173C>T) in the general population?

F8 p.Arg391= (c.1173C>T) is very rare (popmax 0.000248%) (gnomAD).

How is Hemophilia A inherited?

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

F8 p.Arg391=

c.1173C>T · rs1411642179 · VCV914374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000248%)

Conditions

hemophilia A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.28	GERP -2, phastCons 0.89
Overall
CADD	12.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000248%

Overall 0.000248% 3/1,209,706 alleles · very rare exomes 2/1,098,014 · genomes 1/111,692 · joint denominator

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.Arg391=
Coding: c.1173C>T
MANE Select: NM_000132
dbSNP: rs1411642179
Type: single nucleotide variant
Location: chrX:154966524 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 391: a UniProt-annotated variant site (in hema; okayama; moderate/severe; abolishes the normal cleavage by thrombin); a UniProt-annotated variant site (in hema; kumamoto; mild/moderate; abolishes the normal cleavage by thrombin); a UniProt-annotated variant site (in hema; severe; abolishes the normal cleavage by thrombin); a functional site (cleavage; by thrombin)

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.Arg391Cys Pathogenic ★★ ⚠ same residue
F8 p.Arg391His Pathogenic ★★ ⚠ same residue
F8 c.6429+2T>A Pathogenic ★★★ same condition
F8 p.Ala111Thr Likely pathogenic ★★★ same condition
F8 p.Ala2220Pro Pathogenic ★★★ same condition
F8 p.Ala415Asp Likely pathogenic ★★★ same condition
F8 p.Ala415Val Pathogenic ★★★ ⚠ same condition
F8 p.Arg1768His 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-arg391 (accessed [today's date]).

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