Is F9 p.Cys141= (c.423C>T) pathogenic?

F9 p.Cys141= (c.423C>T) is classified Likely benign in F9 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). Ultra-rare (popmax 0.0119%, eas); Associated with thrombophilia, X-linked, due to factor 9 defect.

What condition is associated with F9 p.Cys141= (c.423C>T)?

F9 p.Cys141= (c.423C>T) is associated with thrombophilia, X-linked, due to factor 9 defect, hemophilia B (ClinVar).

How common is F9 p.Cys141= (c.423C>T) in the general population?

F9 p.Cys141= (c.423C>T) is ultra-rare (popmax 0.0119%, eas) (gnomAD).

F9 p.Cys141=

c.423C>T · rs150041781 · VCV1110039

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, eas)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.7	GERP 3, phastCons 1
Overall
CADD	4.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0119% East Asian · 4/33,708 alleles

Filtering AF 0.00396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00236%

Overall 0.00108% 13/1,208,140 alleles · ultra-rare exomes 9/1,096,705 · genomes 4/111,435 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0119%	8,427
Admixed American	0.00219%	45,611
Remaining individualsnot grpmax-eligible	0.0021%	47,555
African / African-American	0.00175%	57,068
European (non-Finnish)	0.000671%	148,978

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.Cys141=
Coding: c.423C>T
MANE Select: NM_000133
dbSNP: rs150041781
Type: single nucleotide variant
Location: chrX:139548394 (GRCh38)
Structure: AlphaFold pLDDT 80.45 · 57 PDB
Residue 141: the egf-like 2 domain; a disulfide bond

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.Cys141Tyr 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-cys141 (accessed [today's date]).

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