Is F5 p.Ser1790Arg (c.5370T>A) pathogenic?

F5 p.Ser1790Arg (c.5370T>A) is classified Conflicting classifications of pathogenicity in F5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-05). AlphaMissense: likely benign (0.1119); Ultra-rare (popmax 0.0165%, mid); Associated with congenital factor V deficiency.

What condition is associated with F5 p.Ser1790Arg (c.5370T>A)?

F5 p.Ser1790Arg (c.5370T>A) is associated with congenital factor V deficiency (ClinVar).

How common is F5 p.Ser1790Arg (c.5370T>A) in the general population?

F5 p.Ser1790Arg (c.5370T>A) is ultra-rare (popmax 0.0165%, mid) (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.Ser1790Arg (c.5370T>A)?

AlphaMissense predicts likely benign (score 0.1119) — an in-silico prediction, not a clinical call.

F5 p.Ser1790Arg

c.5370T>A · rs373101677 · VCV3091474

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1119 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital factor V deficiency

Computational evidence

Protein change
AlphaMissense	0.1119	likely benign
REVEL	0.291	indeterminate
SaProt	LLR -6.18	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.76	GERP -3.2
Regional constraint	o/e 0.84	unconstrained · MANE · 26 kb · p 4.4e-06 · regional, not allelic
Overall
CADD	0.649	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 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00229% 37/1,613,884 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
Admixed American	0.00833%	12,002
European (non-Finnish)	0.00254%	39,328
African / African-American	0.00133%	75,028

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.Ser1790Arg
Coding: c.5370T>A
MANE Select: NM_000130
dbSNP: rs373101677
Type: single nucleotide variant
Location: chr1:169529657 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 1790: an α-helix; the f5/8 type a 3 domain; the plastocyanin-like 6 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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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-ser1790arg (accessed [today's date]).

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