Is F5 p.Pro1449= (c.4347G>A) pathogenic?

F5 p.Pro1449= (c.4347G>A) is classified Conflicting classifications of pathogenicity in F5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0347%, afr); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Pro1449= (c.4347G>A)?

F5 p.Pro1449= (c.4347G>A) is associated with congenital factor V deficiency, thrombophilia due to thrombin defect, Budd-Chiari syndrome (ClinVar).

How common is F5 p.Pro1449= (c.4347G>A) in the general population?

F5 p.Pro1449= (c.4347G>A) is ultra-rare (popmax 0.0347%, afr) (gnomAD).

How is Congenital factor V deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

F5 p.Pro1449=

c.4347G>A · rs145732153 · VCV876842

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0347%, afr)

Conditions

congenital factor V deficiency

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 -1	GERP -3.2
Overall
CADD	2.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0347% African / African-American · 26/74,826 alleles

Filtering AF 0.0243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00713% 115/1,613,714 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0347%	2,878
Remaining individualsnot grpmax-eligible	0.0128%	7,809
East Asian	0.00891%	11,218
European (non-Finnish)	0.00619%	16,163
South Asian	0.00329%	30,361
Admixed American	0.00167%	59,956

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: F5
Protein: p.Pro1449=
Coding: c.4347G>A
MANE Select: NM_000130
dbSNP: rs145732153
Type: single nucleotide variant
Location: chr1:169540743 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1449: the 'b' region; the '35 x 9 aa approximate tandem repeats of [tnp]-l-s-p-d-l-s-q-t' region

Full F5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital factor V deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: thrombophilia due to thrombin defect Budd-Chiari syndrome factor V deficiency

For Congenital factor V deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

F5 p.Pro1449Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1030Ter Pathogenic ★★ same condition
F5 p.Arg146Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1621Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1634Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg740Ter Pathogenic/Likely 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/f5-p-pro1449 (accessed [today's date]).

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