Is F5 p.Ser1430= (c.4290C>T) pathogenic?

F5 p.Ser1430= (c.4290C>T) is classified Likely benign in F5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-12). Very rare (popmax 0.00466%, nfe); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Ser1430= (c.4290C>T)?

F5 p.Ser1430= (c.4290C>T) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Ser1430= (c.4290C>T) in the general population?

F5 p.Ser1430= (c.4290C>T) is very rare (popmax 0.00466%, nfe) (gnomAD).

How is Congenital factor V deficiency inherited?

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

F5 p.Ser1430=

c.4290C>T · rs200497509 · VCV2890519

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00466%, nfe)

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 -1.8	GERP -3.1
Overall
CADD	0.275	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00466% European (non-Finnish) · 55/1,179,286 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.0036% 58/1,612,442 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00466%	21,442
Remaining individualsnot grpmax-eligible	0.0032%	31,223
South Asian	0.0011%	90,874

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.Ser1430=
Coding: c.4290C>T
MANE Select: NM_000130
dbSNP: rs200497509
Type: single nucleotide variant
Location: chr1:169540800 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1430: the 'b' region; the '35 x 9 aa approximate tandem repeats of [tnp]-l-s-p-d-l-s-q-t' region

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

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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-ser1430 (accessed [today's date]).

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