Is F9 p.Asp111= (c.333C>T) pathogenic?

F9 p.Asp111= (c.333C>T) is classified Benign in F9 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-04-17). Very rare (popmax 0.00901%, nfe); Associated with thrombophilia, X-linked, due to factor 9 defect.

What condition is associated with F9 p.Asp111= (c.333C>T)?

F9 p.Asp111= (c.333C>T) is associated with thrombophilia, X-linked, due to factor 9 defect, hemophilia B (ClinVar).

How common is F9 p.Asp111= (c.333C>T) in the general population?

F9 p.Asp111= (c.333C>T) is very rare (popmax 0.00901%, nfe) (gnomAD).

F9 p.Asp111=

c.333C>T · rs139289585 · VCV764284

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00901%, nfe)

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 0.26	GERP 1.5, phastCons 0.98
Overall
CADD	5.486	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00901% European (non-Finnish) · 80/887,921 alleles

Filtering AF 0.00737% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00683%

Overall 0.00709% 85/1,199,542 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00901%	11,099
Admixed American	0.00441%	22,698
Finnishnot grpmax-eligible	0.00218%	45,943
Remaining individualsnot grpmax-eligible	0.00213%	46,937
South Asian	0.00177%	56,589

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.Asp111=
Coding: c.333C>T
MANE Select: NM_000133
dbSNP: rs139289585
Type: single nucleotide variant
Location: chrX:139541131 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 111: a β-strand; a binding site; the egf-like 1; calcium-binding domain; a disulfide bond

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-asp111 (accessed [today's date]).

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