Is F5 p.Gln1345= (c.4035A>G) pathogenic?

F5 p.Gln1345= (c.4035A>G) is classified Conflicting classifications of pathogenicity in F5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-04-01). Rare (popmax 0.275%, afr); Associated with Budd-Chiari syndrome.

What condition is associated with F5 p.Gln1345= (c.4035A>G)?

F5 p.Gln1345= (c.4035A>G) is associated with Budd-Chiari syndrome, thrombophilia due to thrombin defect, congenital factor V deficiency (ClinVar).

How common is F5 p.Gln1345= (c.4035A>G) in the general population?

F5 p.Gln1345= (c.4035A>G) is rare (popmax 0.275%, afr) (gnomAD).

How is Budd-Chiari syndrome inherited?

Typically Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

F5 p.Gln1345=

c.4035A>G · rs886045547 · VCV293601

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.275%, afr)

Conditions

Budd-Chiari syndrome

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 -13	GERP -2.5
Overall
CADD	0.325	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.275% African / African-American · 141/51,310 alleles

Filtering AF 0.238% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.224%

Overall 0.0295% 415/1,408,460 alleles · rare exomes 42/1,317,718 · genomes 373/90,742 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.275%	364
Amishnot grpmax-eligible	0.204%	490
Admixed American	0.091%	1,098
East Asian	0.0769%	1,301
Finnishnot grpmax-eligible	0.0501%	1,998
Ashkenazi Jewishnot grpmax-eligible	0.0266%	3,762
South Asian	0.0199%	5,024
Middle Eastern	0.0198%	5,042
Remaining individualsnot grpmax-eligible	0.0174%	5,732
European (non-Finnish)	0.0141%	7,102

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.Gln1345=
Coding: c.4035A>G
MANE Select: NM_000130
dbSNP: rs886045547
Type: single nucleotide variant
Location: chr1:169541055 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1345: the 'b' region; the '35 x 9 aa approximate tandem repeats of [tnp]-l-s-p-d-l-s-q-t' region; the 'disordered' region

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

Disease context

Budd-Chiari syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: thrombophilia due to thrombin defect congenital factor V deficiency factor V deficiency

For Budd-Chiari syndrome (Orphanet):

Inheritance: Multigenic/multifactorial
Onset: All ages
Prevalence: 1-9 / 100 000 (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-gln1345 (accessed [today's date]).

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