Is F5 p.Arg1908Lys (c.5723G>A) pathogenic?

F5 p.Arg1908Lys (c.5723G>A) is classified Benign/Likely benign in F5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-29). AlphaMissense: likely benign (0.0595); Rare (popmax 0.492%, amr); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Arg1908Lys (c.5723G>A)?

F5 p.Arg1908Lys (c.5723G>A) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Arg1908Lys (c.5723G>A) in the general population?

F5 p.Arg1908Lys (c.5723G>A) is rare (popmax 0.492%, amr) (gnomAD).

How is Congenital factor V deficiency inherited?

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

What do computational predictors say about F5 p.Arg1908Lys (c.5723G>A)?

AlphaMissense predicts likely benign (score 0.0595) — an in-silico prediction, not a clinical call.

F5 p.Arg1908Lys

c.5723G>A · rs191148130 · VCV709012

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0595 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.492%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.0595	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -5.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -1.5, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 26 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	6.197	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.492% Admixed American · 295/59,972 alleles

Filtering AF 0.446% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.428%

Overall 0.0185% 298/1,612,606 alleles · rare exomes 276/1,460,614 · genomes 22/151,992 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.492%	203
Remaining individualsnot grpmax-eligible	0.0032%	31,225
African / African-American	0.00134%	74,860

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.Arg1908Lys
Coding: c.5723G>A
MANE Select: NM_000130
dbSNP: rs191148130
Type: single nucleotide variant
Location: chr1:169524902 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1908: the f5/8 type c 1 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)

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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-arg1908lys (accessed [today's date]).

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