Is F9 p.Ser11Thr (c.31T>A) pathogenic?

F9 p.Ser11Thr (c.31T>A) is classified Conflicting classifications of pathogenicity in F9 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2025-05-08). AlphaMissense: likely benign (0.0683); Very rare (popmax 0.00174%, afr); Associated with hemophilia B.

What condition is associated with F9 p.Ser11Thr (c.31T>A)?

F9 p.Ser11Thr (c.31T>A) is associated with hemophilia B (ClinVar).

How common is F9 p.Ser11Thr (c.31T>A) in the general population?

F9 p.Ser11Thr (c.31T>A) is very rare (popmax 0.00174%, 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.Ser11Thr (c.31T>A)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

F9 p.Ser11Thr

c.31T>A · rs387906480 · VCV10656

Conflicting classifications of pathogenicity No assertion criteria

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00174%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hemophilia B

Computational evidence

Protein change
AlphaMissense	0.0683	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -6.18	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 0.33	GERP -0.79, phastCons 0.21
Regional constraint	o/e 1.17	unconstrained · MANE · 6,280 bp · p 0.32 · regional, not allelic
Overall
CADD	3.804	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 0.00174% African / African-American · 1/57,357 alleles

Overall 0.000889% 1/112,452 alleles · very rare

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.Ser11Thr
Coding: c.31T>A
MANE Select: NM_000133
dbSNP: rs387906480
Type: single nucleotide variant
Location: chrX:139530795 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB

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

For Hemophilia B (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

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-ser11thr (accessed [today's date]).

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