Is F5 c.*1237G>A pathogenic?

F5 c.1237G>A is classified Uncertain significance in F5 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.0193%, eas); Associated with Budd-Chiari syndrome.

How common is F5 c.*1237G>A in the general population?

F5 c.*1237G>A is ultra-rare (popmax 0.0193%, eas) (gnomAD).

How is Budd-Chiari syndrome inherited?

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

F5 c.*1237G>A

Q: What condition is associated with F5 c.*1237G>A?

F5 c.*1237G>A is associated with Budd-Chiari syndrome, thrombophilia due to thrombin defect, thrombophilia due to activated protein C resistance (ClinVar).

rs979200861 · VCV876255

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, eas)

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 -1.6	GERP -0.35
Non-coding constraint	Z 0.55	1 kb window · o/e 0.96 · regional · uncalibrated
Overall
CADD	2.183	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0193% East Asian · 1/5,168 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00792%

Overall 0.0139% 21/151,390 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.144%	692
Remaining individualsnot grpmax-eligible	0.0479%	2,086
East Asiangrpmax	0.0193%	5,168
European (non-Finnish)	0.0177%	5,647
Admixed American	0.0132%	7,591

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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
Coding: c.*1237G>A
MANE Select: NM_000130
dbSNP: rs979200861
Type: single nucleotide variant
Location: chr1:169513076 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB

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 thrombophilia due to activated protein C resistance 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.Arg740Ter Pathogenic/Likely pathogenic ★★ same condition
F5 p.Tyr1730Cys Pathogenic/Likely pathogenic ★★ same condition
F5 c.-110C>A Uncertain significance ★★ same condition
F5 p.Ala38Thr Uncertain significance ★★ ⚠ same condition
F5 p.Arg1715Gln Uncertain significance ★★ ⚠ same condition
F5 p.Arg2055Gln 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-c-star-1237g-a (accessed [today's date]).

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