Is F5 p.Glu763= (c.2289A>G) pathogenic?

F5 p.Glu763= (c.2289A>G) is classified Benign/Likely benign in F5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 9.77%, amr) — too common for a highly-penetrant pathogenic allele; Associated with thrombophilia due to thrombin defect.

What condition is associated with F5 p.Glu763= (c.2289A>G)?

F5 p.Glu763= (c.2289A>G) is associated with thrombophilia due to thrombin defect, congenital factor V deficiency, Budd-Chiari syndrome (ClinVar).

F5 p.Glu763=

Q: How common is F5 p.Glu763= (c.2289A>G) in the general population?

F5 p.Glu763= (c.2289A>G) is common (popmax 9.77%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2289A>G · rs6024 · VCV255195

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 9.77%, amr) — too common for a highly-penetrant pathogenic allele

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 -0.89	GERP -3.6
Overall
CADD	0.522	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.77% Admixed American · 5,863/60,008 alleles

Filtering AF 9.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.48%

Overall 6.11% 98,665/1,614,122 alleles · common exomes 90,301/1,461,822 · genomes 8,364/152,300 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	9.77%	10
Middle Eastern	8.87%	11
Finnishnot grpmax-eligible	8.35%	12
South Asian	7.38%	14
Ashkenazi Jewishnot grpmax-eligible	7.11%	14
Remaining individualsnot grpmax-eligible	6.21%	16
European (non-Finnish)	6.01%	17
East Asian	5.65%	18
African / African-American	1.02%	98
Amishnot grpmax-eligible	0.329%	304

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.Glu763=
Coding: c.2289A>G
MANE Select: NM_000130
dbSNP: rs6024
Type: single nucleotide variant
Location: chr1:169542801 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 763: 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: congenital factor V deficiency 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.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
F5 p.Asp96His 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-glu763 (accessed [today's date]).

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