Is F9 p.Ser365= (c.1095A>G) pathogenic?

F9 p.Ser365= (c.1095A>G) is classified Benign in F9 (ClinVar, Expert panel, 6 submitters; last evaluated 2024-02-09). Low-frequency (popmax 3.27%, afr); Associated with hemophilia B.

What condition is associated with F9 p.Ser365= (c.1095A>G)?

F9 p.Ser365= (c.1095A>G) is associated with hemophilia B, thrombophilia, X-linked, due to factor 9 defect (ClinVar).

How common is F9 p.Ser365= (c.1095A>G) in the general population?

F9 p.Ser365= (c.1095A>G) is low-frequency (popmax 3.27%, afr) (gnomAD).

How is Hemophilia B inherited?

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

F9 p.Ser365=

c.1095A>G · rs112057482 · VCV368002

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.27%, afr)

Conditions

hemophilia B

ClinGen expert panel — Coagulation Factor Deficiency VCEP

Benign for hemophilia B. Applied ACMG criteria (verbatim):

BP7 BP4 BA1

Curation rationale (ClinGen, verbatim)

The NM_000133.3:c.1095A>G variant predicts a synonymous change, Ser365=. It is reported at a high frequency of 0.03271 (622/19015 alleles with 172 hemizygotes) in the African subpopulation in gnomAD v2.1.1, meeting the BA1 cut-off of >=0.0000556. The variant is not predicted to impact splicing, and the nucleotide position at which this variant occurs is not highly conserved, meeting the BP4 and BP7 criteria. To the best of our knowledge, the variant has not been reported in male patients with Hemophilia B. In summary, the variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F9: BA1, BP4, BP7.

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

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 -0.18	GERP -7
Overall
CADD	0.964	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.27% African / African-American · 1,873/57,213 alleles

Filtering AF 3.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.1%

Overall 0.2% 2,419/1,210,305 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.27%	31
Remaining individualsnot grpmax-eligible	0.393%	255
Admixed American	0.332%	301
Middle Eastern	0.207%	484
European (non-Finnish)	0.0211%	4,737
South Asian	0.0158%	6,312

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.Ser365=
Coding: c.1095A>G
MANE Select: NM_000133
dbSNP: rs112057482
Type: single nucleotide variant
Location: chrX:139561780 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 365: the peptidase s1 domain

Full F9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: thrombophilia, X-linked, due to factor 9 defect

For Hemophilia B (Orphanet):

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

Similar variants

F9 p.Ser365Ter Pathogenic ★ 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-ser365 (accessed [today's date]).

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