Is F9 p.Pro101Gln (c.302C>A) pathogenic?

F9 p.Pro101Gln (c.302C>A) is classified Likely pathogenic in F9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). AlphaMissense: likely pathogenic (0.6408); Absent from gnomAD v4.1; Associated with hemophilia B.

What condition is associated with F9 p.Pro101Gln (c.302C>A)?

F9 p.Pro101Gln (c.302C>A) is associated with hemophilia B, thrombophilia, X-linked, due to factor 9 defect (ClinVar).

How common is F9 p.Pro101Gln (c.302C>A) in the general population?

F9 p.Pro101Gln (c.302C>A) is absent from gnomAD v4.1 (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.Pro101Gln (c.302C>A)?

AlphaMissense predicts likely pathogenic (score 0.6408) — an in-silico prediction, not a clinical call.

F9 p.Pro101Gln

c.302C>A · rs2148357901 · VCV1067340

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6408 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,198,077)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hemophilia B

Computational evidence

Protein change
AlphaMissense	0.6408	likely pathogenic ✓ concordant with ClinVar
REVEL	0.951	strongly pathogenic-leaning
SaProt	LLR -12.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 5.3, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 25 kb · p 2.3e-14 · regional, not allelic
Overall
CADD	25.7	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

No allele count reported in gnomAD v4.1 (AN 1,198,077). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: F9
Protein: p.Pro101Gln
Coding: c.302C>A
MANE Select: NM_000133
dbSNP: rs2148357901
Type: single nucleotide variant
Location: chrX:139541100 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 101: a UniProt-annotated variant site (in hemb); 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

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.Pro101Ala Pathogenic ★★ same residue
F9 p.Pro101= Likely benign ★ 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

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-pro101gln (accessed [today's date]).

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