Is F9 p.Ser169= (c.507C>G) pathogenic?

F9 p.Ser169= (c.507C>G) is classified Benign in F9 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-24). Rare (popmax 0.2%, sas); Associated with thrombophilia, X-linked, due to factor 9 defect.

What condition is associated with F9 p.Ser169= (c.507C>G)?

F9 p.Ser169= (c.507C>G) is associated with thrombophilia, X-linked, due to factor 9 defect, hemophilia B (ClinVar).

How common is F9 p.Ser169= (c.507C>G) in the general population?

F9 p.Ser169= (c.507C>G) is rare (popmax 0.2%, sas) (gnomAD).

F9 p.Ser169=

c.507C>G · rs565055999 · VCV794265

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.2%, sas)

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	<0.2	all four deltas below 0.2 · C>A here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.01	GERP -0.31, phastCons 0.77
Overall
CADD	4.572	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.2% South Asian · 113/56,427 alleles

Filtering AF 0.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.159%

Overall 0.00952% 115/1,208,011 alleles · rare exomes 110/1,096,134 · genomes 5/111,877 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.2%	499
Remaining individualsnot grpmax-eligible	0.00421%	23,774

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.Ser169=
Coding: c.507C>G
MANE Select: NM_000133
dbSNP: rs565055999
Type: single nucleotide variant
Location: chrX:139548478 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 169: a UniProt-annotated variant site (in hemb); the egf-like 2 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.Ser169Pro Likely 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
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-ser169 (accessed [today's date]).

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