Is F5 p.His710Arg (c.2129A>G) pathogenic?

F5 p.His710Arg (c.2129A>G) is classified Benign/Likely benign in F5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0657); Low-frequency (popmax 1.21%, afr); Associated with congenital factor V deficiency.

What condition is associated with F5 p.His710Arg (c.2129A>G)?

F5 p.His710Arg (c.2129A>G) is associated with congenital factor V deficiency, thrombophilia due to activated protein C resistance, Budd-Chiari syndrome (ClinVar).

How common is F5 p.His710Arg (c.2129A>G) in the general population?

F5 p.His710Arg (c.2129A>G) is low-frequency (popmax 1.21%, afr) (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.His710Arg (c.2129A>G)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

F5 p.His710Arg

c.2129A>G · rs115954845 · VCV716055

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.21%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -4.75	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 -6.5	GERP -3.8
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.00099 · regional, not allelic
Overall
CADD	0.003	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 1.21% African / African-American · 907/75,044 alleles

Filtering AF 1.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.12%

Overall 0.0673% 1,087/1,614,128 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.21%	83
Middle Eastern	0.165%	606
Remaining individualsnot grpmax-eligible	0.118%	845
Admixed American	0.113%	883
South Asian	0.011%	9,108
European (non-Finnish)	0.00153%	65,554

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.His710Arg
Coding: c.2129A>G
MANE Select: NM_000130
dbSNP: rs115954845
Type: single nucleotide variant
Location: chr1:169542961 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 710: a β-strand; the 'b' 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

Also linked: thrombophilia due to activated protein C resistance Budd-Chiari syndrome pregnancy loss, recurrent, susceptibility to, 1 factor V deficiency ischemic stroke

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.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-his710arg (accessed [today's date]).

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