Is F5 p.Pro1440fs (c.4317_4318del) pathogenic?

F5 p.Pro1440fs (c.43174318del) is classified Pathogenic in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-09). Very rare (popmax 8.47e-05%, nfe); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Pro1440fs (c.4317_4318del)?

F5 p.Pro1440fs (c.4317_4318del) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Pro1440fs (c.4317_4318del) in the general population?

F5 p.Pro1440fs (c.4317_4318del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Congenital factor V deficiency inherited?

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

F5 p.Pro1440fs

c.4317_4318del · rs1659815819 · VCV2746047

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 13 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	GERP -0.29, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,978 alleles

Overall 6.2e-05% 1/1,614,008 alleles · very rare exomes 1/1,461,780 · genomes 0/152,228 · joint denominator

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.Pro1440fs
Coding: c.4317_4318del
MANE Select: NM_000130
dbSNP: rs1659815819
Type: Microsatellite
Location: chr1:169540772 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1440: 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

For Congenital factor V deficiency (Orphanet):

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

Similar variants

F5 p.1233PDLSHTTLS[1] Uncertain significance ★★ same condition
F5 p.Ser1304fs Pathogenic ★ same condition
F5 p.Thr915fs Pathogenic ★ same condition
F5 c.5600-16_5600-14del Likely benign ★ same condition
F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
F5 c.4962_4971+3del Likely pathogenic ★★ same condition
F5 p.Arg1030Ter Pathogenic ★★ same condition
F5 p.Arg146Ter 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-pro1440fs (accessed [today's date]).

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