Is F9 p.Pro197Ser (c.589C>T) pathogenic?

F9 p.Pro197Ser (c.589C>T) is classified Likely benign in F9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-03). AlphaMissense: likely benign (0.0598); Very rare (popmax 0.00173%, afr); Associated with hemophilia B.

What condition is associated with F9 p.Pro197Ser (c.589C>T)?

F9 p.Pro197Ser (c.589C>T) is associated with hemophilia B, thrombophilia, X-linked, due to factor 9 defect (ClinVar).

How common is F9 p.Pro197Ser (c.589C>T) in the general population?

F9 p.Pro197Ser (c.589C>T) is very rare (popmax 0.00173%, afr) (gnomAD).

How is Hemophilia B inherited?

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

What do computational predictors say about F9 p.Pro197Ser (c.589C>T)?

AlphaMissense predicts likely benign (score 0.0598) — an in-silico prediction, not a clinical call.

F9 p.Pro197Ser

c.589C>T · rs867548424 · VCV1959260

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0598 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00173%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hemophilia B

Computational evidence

Protein change
AlphaMissense	0.0598	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -5.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.073	GERP -3, phastCons 0.002
Regional constraint	o/e 0.57	unconstrained · MANE · 25 kb · p 2.3e-14 · regional, not allelic
Overall
CADD	0.029	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00173% African / African-American · 1/57,790 alleles

Overall 0.000182% 2/1,097,410 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00173%	57,790
European (non-Finnish)	0.000112%	894,807

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.Pro197Ser
Coding: c.589C>T
MANE Select: NM_000133
dbSNP: rs867548424
Type: single nucleotide variant
Location: chrX:139551130 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 197: a disulfide bond

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 p.Pro197Leu Uncertain significance ★ ⚠ same residue
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

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-pro197ser (accessed [today's date]).

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