Is F5 p.Arg513= (c.1539A>G) pathogenic?

F5 p.Arg513= (c.1539A>G) is classified Benign/Likely benign in F5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-05-01). Rare (popmax 0.446%, afr); Associated with Inborn genetic diseases.

What condition is associated with F5 p.Arg513= (c.1539A>G)?

F5 p.Arg513= (c.1539A>G) is associated with Inborn genetic diseases, factor V deficiency (ClinVar).

How common is F5 p.Arg513= (c.1539A>G) in the general population?

F5 p.Arg513= (c.1539A>G) is rare (popmax 0.446%, afr) (gnomAD).

F5 p.Arg513=

c.1539A>G · rs140627208 · VCV786473

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.446%, afr)

Conditions

Inborn genetic diseases

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 0.55	GERP -2.5, phastCons 1
Overall
CADD	8.078	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.446% African / African-American · 335/75,056 alleles

Filtering AF 0.407% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.392%

Overall 0.0265% 427/1,614,150 alleles · rare exomes 229/1,461,832 · genomes 198/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.446%	224
Admixed American	0.055%	1,819
Remaining individualsnot grpmax-eligible	0.0144%	6,945
European (non-Finnish)	0.00424%	23,600

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.Arg513=
Coding: c.1539A>G
MANE Select: NM_000130
dbSNP: rs140627208
Type: single nucleotide variant
Location: chr1:169549873 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 513: a UniProt-annotated variant site (in); an α-helix; the f5/8 type a 2 domain; the plastocyanin-like 3 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: factor V deficiency

Similar variants

F5 c.1297-2A>G Pathogenic/Likely 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.Arg1715Gln Uncertain significance ★★ ⚠ same condition
F5 p.Arg2055Gln Uncertain significance ★★ ⚠ same condition
F5 p.Arg376Ser Uncertain significance ★★ ⚠ same condition
F5 p.Arg441His 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-p-arg513 (accessed [today's date]).

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