Is F9 p.Val273= (c.819T>C) pathogenic?

F9 p.Val273= (c.819T>C) is classified Benign/Likely benign in F9 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-31). Rare (popmax 0.208%, mid); Associated with thrombophilia, X-linked, due to factor 9 defect.

What condition is associated with F9 p.Val273= (c.819T>C)?

F9 p.Val273= (c.819T>C) is associated with thrombophilia, X-linked, due to factor 9 defect, hemophilia B (ClinVar).

How common is F9 p.Val273= (c.819T>C) in the general population?

F9 p.Val273= (c.819T>C) is rare (popmax 0.208%, mid) (gnomAD).

F9 p.Val273=

c.819T>C · rs1800455 · VCV10600

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.208%, 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 1.2	GERP 4.1, phastCons 1
Overall
CADD	1.623	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.208% Middle Eastern · 9/4,319 alleles

Filtering AF 0.175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.172%

Overall 0.161% 1,925/1,198,637 alleles · rare exomes 1,799/1,086,671 · genomes 126/111,966 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.292%	343
Ashkenazi Jewishnot grpmax-eligible	0.237%	422
Middle Easterngrpmax	0.208%	480
European (non-Finnish)	0.183%	548
Remaining individualsnot grpmax-eligible	0.18%	556
South Asian	0.15%	665
Finnishnot grpmax-eligible	0.0925%	1,082
Admixed American	0.0612%	1,634
African / African-American	0.0105%	9,512

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val273=
Coding: c.819T>C
MANE Select: NM_000133
dbSNP: rs1800455
Type: single nucleotide variant
Location: chrX:139560836 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 273: an α-helix; 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-val273 (accessed [today's date]).

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