Is F9 p.His282Arg (c.845A>G) pathogenic?

F9 p.His282Arg (c.845A>G) is classified Conflicting classifications of pathogenicity in F9 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-05-29). AlphaMissense: likely benign (0.1387); Very rare (popmax 0.00359%, nfe); Associated with hemophilia A.

What condition is associated with F9 p.His282Arg (c.845A>G)?

F9 p.His282Arg (c.845A>G) is associated with hemophilia A, hemophilia B (ClinVar).

How common is F9 p.His282Arg (c.845A>G) in the general population?

F9 p.His282Arg (c.845A>G) is very rare (popmax 0.00359%, nfe) (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 F9 p.His282Arg (c.845A>G)?

AlphaMissense predicts likely benign (score 0.1387) — an in-silico prediction, not a clinical call.

F9 p.His282Arg

c.845A>G · rs753654616 · VCV627146

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1387 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00359%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hemophilia A

Computational evidence

Protein change
AlphaMissense	0.1387	likely benign
REVEL	0.707	pathogenic-leaning
SaProt	LLR -12.31	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 4.9, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 25 kb · p 2.3e-14 · regional, not allelic
Overall
CADD	18.66	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

Grpmax group 0.00359% European (non-Finnish) · 32/890,491 alleles

Filtering AF 0.0026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00222%

Overall 0.00303% 33/1,090,681 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00359%	27,828
Remaining individualsnot grpmax-eligible	0.00211%	47,384

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: F9
Protein: p.His282Arg
Coding: c.845A>G
MANE Select: NM_000133
dbSNP: rs753654616
Type: single nucleotide variant
Location: chrX:139561530 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 282: a β-strand; a disulfide bond; the peptidase s1 domain

Full F9 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

Also linked: hemophilia B

For Hemophilia A (Orphanet):

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

Similar variants

F9 p.His282Tyr Likely benign ★ same residue
F9 c.520+13A>G Pathogenic ★★★ same condition
F9 c.88+1G>A Pathogenic ★★★ same condition
F9 c.88+5G>T Likely pathogenic ★★★ same condition
F9 p.Ala279Thr Pathogenic ★★★ ⚠ same condition
F9 p.Ala337Pro Likely pathogenic ★★★ same condition
F9 p.Ala337Thr Pathogenic ★★★ ⚠ same condition
F9 p.Ala337Val 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/f9-p-his282arg (accessed [today's date]).

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