Is F9 c.252+14C>T pathogenic?

F9 c.252+14C>T is classified Likely benign in F9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-31). Ultra-rare (popmax 0.0106%, sas); Associated with hemophilia B.

What condition is associated with F9 c.252+14C>T?

F9 c.252+14C>T is associated with hemophilia B, thrombophilia, X-linked, due to factor 9 defect (ClinVar).

How common is F9 c.252+14C>T in the general population?

F9 c.252+14C>T is ultra-rare (popmax 0.0106%, sas) (gnomAD).

How is Hemophilia B inherited?

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

F9 c.252+14C>T

rs756055116 · VCV2932713

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, sas)

Conditions

hemophilia B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +14	near-intronic (+14 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.87	GERP -2.1
Non-coding constraint	—	not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained
Overall
CADD	0.919	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0106% South Asian · 6/56,713 alleles

Filtering AF 0.00459% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000641% 7/1,091,675 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0106%	9,452
European (non-Finnish)	0.000112%	889,933

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
Coding: c.252+14C>T
MANE Select: NM_000133
dbSNP: rs756055116
Type: single nucleotide variant
Location: chrX:139537187 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB

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-c-252-plus-14c-t (accessed [today's date]).

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