Is F5 p.Pro809Ser (c.2425C>T) pathogenic?

F5 p.Pro809Ser (c.2425C>T) is classified Benign/Likely benign in F5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.095); Common (popmax 8.07%, afr) — too common for a highly-penetrant pathogenic allele; Associated with congenital factor V deficiency.

What condition is associated with F5 p.Pro809Ser (c.2425C>T)?

F5 p.Pro809Ser (c.2425C>T) is associated with congenital factor V deficiency, thrombophilia due to thrombin defect, Budd-Chiari syndrome (ClinVar).

How is Congenital factor V deficiency inherited?

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

What do computational predictors say about F5 p.Pro809Ser (c.2425C>T)?

AlphaMissense predicts likely benign (score 0.095) — an in-silico prediction, not a clinical call.

F5 p.Pro809Ser

Q: How common is F5 p.Pro809Ser (c.2425C>T) in the general population?

F5 p.Pro809Ser (c.2425C>T) is common (popmax 8.07%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2425C>T · rs6031 · VCV255198

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.095 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.07%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.095	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -5.25	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 0.83	GERP 0.11
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	2.895	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 8.07% African / African-American · 6,054/75,002 alleles

Filtering AF 7.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.83%

Overall 0.429% 6,930/1,614,062 alleles · common exomes 3,489/1,461,822 · genomes 3,441/152,240 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.07%	12
Remaining individualsnot grpmax-eligible	0.552%	181
Admixed American	0.547%	183
Middle Eastern	0.462%	216
European (non-Finnish)	0.014%	7,151
South Asian	0.011%	9,107

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.Pro809Ser
Coding: c.2425C>T
MANE Select: NM_000130
dbSNP: rs6031
Type: single nucleotide variant
Location: chr1:169542665 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 809: a UniProt-annotated variant site (in); the 'b' 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.Pro809= Likely benign ★★ 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-pro809ser (accessed [today's date]).

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