Is F9 p.Thr16= (c.48C>A) pathogenic?

F9 p.Thr16= (c.48C>A) is classified Benign in F9 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-10). Ultra-rare (popmax 0.069%, mid); Associated with thrombophilia, X-linked, due to factor 9 defect.

What condition is associated with F9 p.Thr16= (c.48C>A)?

F9 p.Thr16= (c.48C>A) is associated with thrombophilia, X-linked, due to factor 9 defect, hemophilia B (ClinVar).

How common is F9 p.Thr16= (c.48C>A) in the general population?

F9 p.Thr16= (c.48C>A) is ultra-rare (popmax 0.069%, mid) (gnomAD).

F9 p.Thr16=

c.48C>A · rs768833956 · VCV1164738

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.069%, mid)

Conditions

thrombophilia, X-linked, due to factor 9 defect

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 2.6	GERP 3.4, phastCons 1
Overall
CADD	10.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.069% Middle Eastern · 3/4,350 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00997%

Overall 0.000365% 4/1,096,957 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.069%	1,450
Remaining individualsnot grpmax-eligible	0.0021%	47,599

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.Thr16=
Coding: c.48C>A
MANE Select: NM_000133
dbSNP: rs768833956
Type: single nucleotide variant
Location: chrX:139530812 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB

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

Disease context

thrombophilia, X-linked, due to factor 9 defect — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hemophilia B

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-thr16 (accessed [today's date]).

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