Is F9 p.Asn36Asp (c.106A>G) pathogenic?

F9 p.Asn36Asp (c.106A>G) is classified Likely benign in F9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-03). AlphaMissense: likely benign (0.0877); Very rare (popmax 0.00101%, nfe); Associated with hemophilia B.

What condition is associated with F9 p.Asn36Asp (c.106A>G)?

F9 p.Asn36Asp (c.106A>G) is associated with hemophilia B, thrombophilia, X-linked, due to factor 9 defect (ClinVar).

How common is F9 p.Asn36Asp (c.106A>G) in the general population?

F9 p.Asn36Asp (c.106A>G) is very rare (popmax 0.00101%, nfe) (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.Asn36Asp (c.106A>G)?

AlphaMissense predicts likely benign (score 0.0877) — an in-silico prediction, not a clinical call.

F9 p.Asn36Asp

c.106A>G · rs1169714103 · VCV1078704

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0877 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00101%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hemophilia B

Computational evidence

Protein change
AlphaMissense	0.0877	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -3.92	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 7.7	GERP 4, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 6,280 bp · p 0.32 · regional, not allelic
Overall
CADD	18.06	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 0.00101% European (non-Finnish) · 9/893,485 alleles

Filtering AF 0.000474% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000343%

Overall 0.000829% 10/1,206,671 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00211%	47,462
European (non-Finnish)grpmax	0.00101%	99,276

Remaining individuals 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.Asn36Asp
Coding: c.106A>G
MANE Select: NM_000133
dbSNP: rs1169714103
Type: single nucleotide variant
Location: chrX:139537027 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 36: an α-helix

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.Asn36= 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
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-asn36asp (accessed [today's date]).

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