Is F8 p.Arg301His (c.902G>A) pathogenic?

F8 p.Arg301His (c.902G>A) is classified Pathogenic in F8 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-03-06). AlphaMissense: likely benign (0.2995); Absent from gnomAD v4.1; Associated with severe hemophilia A.

What condition is associated with F8 p.Arg301His (c.902G>A)?

F8 p.Arg301His (c.902G>A) is associated with severe hemophilia A, hemophilia A (ClinVar).

How common is F8 p.Arg301His (c.902G>A) in the general population?

F8 p.Arg301His (c.902G>A) is absent from gnomAD v4.1 (gnomAD).

How is Hemophilia A inherited?

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

What do computational predictors say about F8 p.Arg301His (c.902G>A)?

AlphaMissense predicts likely benign (score 0.2995) — an in-silico prediction, not a clinical call.

F8 p.Arg301His

c.902G>A · rs137852403 · VCV10192

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

severe hemophilia A

Computational evidence

Protein change
AlphaMissense	0.2995	likely benign ⚠ discordant with ClinVar
REVEL	0.848	moderately pathogenic-leaning
SaProt	LLR -9.30	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 53 kb · p 1.5e-11 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: F8
Protein: p.Arg301His
Coding: c.902G>A
MANE Select: NM_000132
dbSNP: rs137852403
Type: single nucleotide variant
Location: chrX:154969438 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 301: a UniProt-annotated variant site (in hema; severe/mild); a UniProt-annotated variant site (in hema; severe); a β-strand; the f5/8 type a 1 domain; the plastocyanin-like 2 domain

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

Disease context

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

Also linked: hemophilia A

For Hemophilia A (Orphanet):

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

Similar variants

F8 p.Arg301Cys Pathogenic ★ same residue
F8 p.Arg301Leu Pathogenic ★ ⚠ same residue
F8 p.Arg301= Likely benign ★ 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

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-arg301his (accessed [today's date]).

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