Is F9 p.Ile17= (c.51C>T) pathogenic?

F9 p.Ile17= (c.51C>T) is classified Benign in F9 (ClinVar, Expert panel, 3 submitters; last evaluated 2024-02-09). Rare (popmax 0.326%, amr); Associated with hemophilia B.

What condition is associated with F9 p.Ile17= (c.51C>T)?

F9 p.Ile17= (c.51C>T) is associated with hemophilia B, thrombophilia, X-linked, due to factor 9 defect (ClinVar).

How common is F9 p.Ile17= (c.51C>T) in the general population?

F9 p.Ile17= (c.51C>T) is rare (popmax 0.326%, amr) (gnomAD).

How is Hemophilia B inherited?

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

F9 p.Ile17=

c.51C>T · rs774612303 · VCV697610

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.326%, amr)

Conditions

hemophilia B

ClinGen expert panel — Coagulation Factor Deficiency VCEP

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

BA1

Curation rationale (ClinGen, verbatim)

The NM_000133.4:c.51C>T (p.Ile17=) synonymous variant is reported at a high MAF of 0.004462 (125/28017 alleles with 31 hemizygotes) in the Latino population of gnomAD v2.1.1, meeting the BA1 cut-off of >/= 0.0000556. In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency VCEP for F9: BA1.

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 0.33	GERP 0.48, phastCons 0.99
Overall
CADD	9.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.326% Admixed American · 149/45,764 alleles

Filtering AF 0.283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.267%

Overall 0.0128% 155/1,209,372 alleles · rare exomes 143/1,096,890 · genomes 12/112,482 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.326%	307
Remaining individualsnot grpmax-eligible	0.00631%	15,853
European (non-Finnish)	0.000335%	298,092

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.Ile17=
Coding: c.51C>T
MANE Select: NM_000133
dbSNP: rs774612303
Type: single nucleotide variant
Location: chrX:139530815 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 17: a UniProt-annotated variant site (in hemb; severe; uk 22)

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 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
F9 p.Arg191His 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-ile17 (accessed [today's date]).

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