Is F2 p.Val185fs (c.552del) pathogenic?

F2 p.Val185fs (c.552del) is classified Pathogenic in F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Associated with congenital prothrombin deficiency.

What condition is associated with F2 p.Val185fs (c.552del)?

F2 p.Val185fs (c.552del) is associated with congenital prothrombin deficiency (ClinVar).

How is Congenital factor II deficiency inherited?

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

F2 p.Val185fs

c.552del · VCV4686696

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

congenital prothrombin deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: F2
Protein: p.Val185fs
Coding: c.552del
MANE Select: NM_000506
Type: Deletion
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 185: the kringle 1 domain

Full F2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Congenital factor II deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

F2 p.Val185= Likely benign ★ same residue
F2 p.Asp308fs Pathogenic ★ same condition
F2 p.His605fs Conflicting classifications of pathogenicity ★ same condition
F2 c.1131-18_1131-15del Likely benign ★ same condition
F2 c.80-13del Benign ★ same condition
F2 p.Arg461Trp Pathogenic/Likely pathogenic ★★ same condition
F2 p.Arg500Gln Pathogenic ★★ ⚠ same condition
F2 p.Arg581Cys 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/f2-p-val185fs (accessed [today's date]).

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