Is F5 p.Glu595= (c.1785G>A) pathogenic?

F5 p.Glu595= (c.1785G>A) is classified Conflicting classifications of pathogenicity in F5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-05). Rare (popmax 0.247%, afr); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Glu595= (c.1785G>A)?

F5 p.Glu595= (c.1785G>A) is associated with congenital factor V deficiency, thrombophilia due to thrombin defect, Budd-Chiari syndrome (ClinVar).

How common is F5 p.Glu595= (c.1785G>A) in the general population?

F5 p.Glu595= (c.1785G>A) is rare (popmax 0.247%, afr) (gnomAD).

How is Congenital factor V deficiency inherited?

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

F5 p.Glu595=

c.1785G>A · rs112333778 · VCV293624

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.247%, afr)

Conditions

congenital factor V deficiency

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 -1	GERP -3.5, phastCons 0.001
Overall
CADD	0.945	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.247% African / African-American · 185/75,050 alleles

Filtering AF 0.217% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.206%

Overall 0.0126% 203/1,614,006 alleles · rare exomes 107/1,461,688 · genomes 96/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.247%	406
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.01%	9,998
South Asian	0.0011%	91,072

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.Glu595=
Coding: c.1785G>A
MANE Select: NM_000130
dbSNP: rs112333778
Type: single nucleotide variant
Location: chr1:169544486 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 595: the plastocyanin-like 4 domain; a turn; the f5/8 type a 2 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

Also linked: thrombophilia due to thrombin defect Budd-Chiari syndrome factor V deficiency

For Congenital factor V deficiency (Orphanet):

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

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-glu595 (accessed [today's date]).

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