Is F5 p.Ala1568fs (c.4699_4702dup) pathogenic?

F5 p.Ala1568fs (c.46994702dup) is classified Pathogenic in F5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1999-09-01). Very rare (popmax 0.000763%, nfe); Associated with factor V deficiency.

What condition is associated with F5 p.Ala1568fs (c.4699_4702dup)?

F5 p.Ala1568fs (c.4699_4702dup) is associated with factor V deficiency (ClinVar).

How common is F5 p.Ala1568fs (c.4699_4702dup) in the general population?

F5 p.Ala1568fs (c.4699_4702dup) is very rare (popmax 0.000763%, nfe) (gnomAD).

F5 p.Ala1568fs

c.4699_4702dup · rs773569662 · VCV647

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Conditions

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 9.9	GERP 1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,936 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,724 alleles · very rare

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.Ala1568fs
Coding: c.4699_4702dup
MANE Select: NM_000130
dbSNP: rs773569662
Type: Duplication
Location: chr1:169540387 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1568: the 'b' region

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

Disease context

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

Similar variants

F5 p.His611fs Pathogenic/Likely pathogenic ★★ same condition
F5 p.Ala1568Ser Uncertain significance ★ ⚠ same residue
F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Ile847fs Pathogenic/Likely pathogenic ★★ same condition
F5 p.Ser955fs Pathogenic/Likely pathogenic ★★ same condition
F5 p.Tyr1730Cys Pathogenic/Likely pathogenic ★★ same condition
F5 c.-110C>A Uncertain significance ★★ 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-ala1568fs (accessed [today's date]).

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