Is F9 p.Ala397= (c.1191T>C) pathogenic?

F9 p.Ala397= (c.1191T>C) is classified Likely benign in F9 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-14). Very rare (popmax 0.000112%, nfe); Associated with thrombophilia, X-linked, due to factor 9 defect.

What condition is associated with F9 p.Ala397= (c.1191T>C)?

F9 p.Ala397= (c.1191T>C) is associated with thrombophilia, X-linked, due to factor 9 defect, hemophilia B (ClinVar).

How common is F9 p.Ala397= (c.1191T>C) in the general population?

F9 p.Ala397= (c.1191T>C) is very rare (popmax 0.000112%, nfe) (gnomAD).

F9 p.Ala397=

c.1191T>C · rs777757344 · VCV1668356

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

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 -5.8	GERP -4.6
Overall
CADD	5.663	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,549 alleles

Overall 9.11e-05% 1/1,098,198 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.Ala397=
Coding: c.1191T>C
MANE Select: NM_000133
dbSNP: rs777757344
Type: single nucleotide variant
Location: chrX:139561876 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 397: a UniProt-annotated variant site (in hemb; mild; hong kong-11); a β-strand; 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 p.Ala397Val Pathogenic ★ same residue
F9 p.Ala397Pro Pathogenic 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-ala397 (accessed [today's date]).

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