Is F9 p.Val278= (c.834C>T) pathogenic?

F9 p.Val278= (c.834C>T) is classified Benign in F9 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-21). Very rare (popmax 0.00538%, sas); Associated with thrombophilia, X-linked, due to factor 9 defect.

What condition is associated with F9 p.Val278= (c.834C>T)?

F9 p.Val278= (c.834C>T) is associated with thrombophilia, X-linked, due to factor 9 defect, hemophilia B (ClinVar).

How common is F9 p.Val278= (c.834C>T) in the general population?

F9 p.Val278= (c.834C>T) is very rare (popmax 0.00538%, sas) (gnomAD).

F9 p.Val278=

c.834C>T · rs199844858 · VCV700810

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00538%, sas)

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 -3.6	GERP -10
Overall
CADD	0.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00538% South Asian · 3/55,735 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000696%

Overall 0.00112% 13/1,164,839 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00538%	18,578
African / African-American	0.00355%	28,158
Finnishnot grpmax-eligible	0.00216%	46,339
European (non-Finnish)	0.000819%	122,055

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.Val278=
Coding: c.834C>T
MANE Select: NM_000133
dbSNP: rs199844858
Type: single nucleotide variant
Location: chrX:139560851 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 278: a β-strand; a disulfide bond; the peptidase s1 domain

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-val278 (accessed [today's date]).

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