Is F5 p.Pro1087= (c.3261C>G) pathogenic?

F5 p.Pro1087= (c.3261C>G) is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Ultra-rare (popmax 0.0165%, mid); Associated with thrombophilia due to thrombin defect.

What condition is associated with F5 p.Pro1087= (c.3261C>G)?

F5 p.Pro1087= (c.3261C>G) is associated with thrombophilia due to thrombin defect, Budd-Chiari syndrome, factor V deficiency (ClinVar).

How common is F5 p.Pro1087= (c.3261C>G) in the general population?

F5 p.Pro1087= (c.3261C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

F5 p.Pro1087=

c.3261C>G · rs886045549 · VCV293612

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

thrombophilia due to thrombin defect

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 0.9	GERP -3.3, phastCons 0.25
Overall
CADD	2.494	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Overall 6.2e-05% 1/1,614,092 alleles · ultra-rare exomes 1/1,461,818 · genomes 0/152,274 · 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.Pro1087=
Coding: c.3261C>G
MANE Select: NM_000130
dbSNP: rs886045549
Type: single nucleotide variant
Location: chr1:169541829 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1087: the 'b' region

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

Disease context

thrombophilia due to thrombin defect — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Budd-Chiari syndrome factor V deficiency

Similar variants

F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
F5 p.Arg1030Ter Pathogenic ★★ same condition
F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Tyr1730Cys Pathogenic/Likely pathogenic ★★ same condition
F5 c.-110C>A Uncertain significance ★★ same condition
F5 p.Arg1715Gln Uncertain significance ★★ ⚠ same condition
F5 p.Arg2055Gln Uncertain significance ★★ ⚠ same condition
F5 p.Arg376Ser 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-pro1087 (accessed [today's date]).

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