Is F5 p.Asn55= (c.165T>C) pathogenic?

F5 p.Asn55= (c.165T>C) is classified Conflicting classifications of pathogenicity in F5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-28). Very rare (popmax 0.0051%, nfe); Associated with factor V deficiency.

What condition is associated with F5 p.Asn55= (c.165T>C)?

F5 p.Asn55= (c.165T>C) is associated with factor V deficiency, thrombophilia due to thrombin defect, congenital factor V deficiency (ClinVar).

How common is F5 p.Asn55= (c.165T>C) in the general population?

F5 p.Asn55= (c.165T>C) is very rare (popmax 0.0051%, nfe) (gnomAD).

F5 p.Asn55=

c.165T>C · rs781434840 · VCV293641

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0051%, nfe)

Conditions

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 1.7	GERP 2.1, phastCons 0.38
Overall
CADD	7.247	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0051% European (non-Finnish) · 56/1,098,114 alleles

Filtering AF 0.00403% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.00395% 60/1,518,362 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0051%	19,609
Remaining individualsnot grpmax-eligible	0.00509%	19,650
African / African-American	0.00137%	73,150

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.Asn55=
Coding: c.165T>C
MANE Select: NM_000130
dbSNP: rs781434840
Type: single nucleotide variant
Location: chr1:169582516 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.57 · 23 PDB
Residue 55: an α-helix; the f5/8 type a 1 domain; the plastocyanin-like 1 domain

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

Disease context

factor V deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: thrombophilia due to thrombin defect congenital factor V deficiency Budd-Chiari syndrome

Similar variants

F5 p.Asn55Asp Uncertain significance ★ ⚠ same residue
F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same condition
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

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-asn55 (accessed [today's date]).

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