Is F5 p.Arg534Ter (c.1600C>T) pathogenic?

F5 p.Arg534Ter (c.1600C>T) is classified Pathogenic in F5 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-11-29). Very rare (popmax 0.00669%, eas); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Arg534Ter (c.1600C>T)?

F5 p.Arg534Ter (c.1600C>T) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Arg534Ter (c.1600C>T) in the general population?

F5 p.Arg534Ter (c.1600C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

How is Congenital factor V deficiency inherited?

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

F5 p.Arg534Ter

c.1600C>T · rs770011773 · VCV1452773

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

congenital factor V deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 25
Splicing
SpliceAI	Δ0.99	donor gain · deltas
Pangolin	Δ0.85	gain · loss 0.68 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.1	GERP -1.3, phastCons 0.99
Overall
CADD	49.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,860 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000868% 14/1,612,748 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,953
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,592
Admixed American	0.00167%	60,006
South Asian	0.0011%	91,064
European (non-Finnish)	0.000679%	147,373

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.Arg534Ter
Coding: c.1600C>T
MANE Select: NM_000130
dbSNP: rs770011773
Type: single nucleotide variant
Location: chr1:169549812 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 534: a UniProt-annotated variant site (in thph2; factor v leiden; risk factor for budd-chiari syndrome; risk factor for ischemic stroke); a β-strand; a functional site (cleavage; by activated protein c); 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

For Congenital factor V deficiency (Orphanet):

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

Similar variants

F5 p.Arg534= Conflicting classifications of pathogenicity ★ same residue
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

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-arg534ter (accessed [today's date]).

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