Is F5 p.Ser1802fs (c.5403dup) pathogenic?

F5 p.Ser1802fs (c.5403dup) is classified Pathogenic/Likely pathogenic in F5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-15). Very rare (popmax 0.00167%, amr); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Ser1802fs (c.5403dup)?

F5 p.Ser1802fs (c.5403dup) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Ser1802fs (c.5403dup) in the general population?

F5 p.Ser1802fs (c.5403dup) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Congenital factor V deficiency inherited?

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

F5 p.Ser1802fs

c.5403dup · rs757917115 · VCV524063

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

congenital factor V deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.17, phastCons 1
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,950 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,424 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,950
European (non-Finnish)	0.000339%	294,918

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.Ser1802fs
Coding: c.5403dup
MANE Select: NM_000130
dbSNP: rs757917115
Type: Duplication
Location: chr1:169529623 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1802: the f5/8 type a 3 domain; the plastocyanin-like 6 domain

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

For Congenital factor V deficiency (Orphanet):

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

Similar variants

F5 p.His611fs Pathogenic/Likely pathogenic ★★ same condition
F5 p.Ser1680fs Pathogenic ★★ same condition
F5 p.Lys327Ter Pathogenic ★ same condition
F5 p.Pro1404fs Pathogenic ★ same condition
F5 p.Ser1362fs Pathogenic ★ same condition
F5 p.Ser158delinsLysTyrGlnTer Pathogenic ★ same condition
F5 c.1119-14dup Benign ★ same condition
F5 c.1612-10dup Benign ★ 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-ser1802fs (accessed [today's date]).

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