Is F2 p.Pro160= (c.480C>T) pathogenic?

F2 p.Pro160= (c.480C>T) is classified Benign/Likely benign in F2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 14.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with congenital prothrombin deficiency.

What condition is associated with F2 p.Pro160= (c.480C>T)?

F2 p.Pro160= (c.480C>T) is associated with congenital prothrombin deficiency, thrombophilia due to thrombin defect (ClinVar).

How is Congenital factor II deficiency inherited?

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

F2 p.Pro160=

Q: How common is F2 p.Pro160= (c.480C>T) in the general population?

F2 p.Pro160= (c.480C>T) is common (popmax 14.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.480C>T · rs3136452 · VCV256316

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 14.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

congenital prothrombin deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.3	GERP -3.8
Overall
CADD	0.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.1% African / African-American · 10,559/74,992 alleles

Filtering AF 13.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.8%

Overall 0.759% 12,250/1,614,054 alleles · common exomes 6,144/1,461,840 · genomes 6,106/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.1%	7
Amishnot grpmax-eligible	1.64%	61
Admixed American	1.12%	89
Remaining individualsnot grpmax-eligible	1.05%	95
Middle Eastern	0.577%	173
Ashkenazi Jewishnot grpmax-eligible	0.216%	463
South Asian	0.0373%	2,679
European (non-Finnish)	0.018%	5,566
East Asian	0.00446%	22,430

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: F2
Protein: p.Pro160=
Coding: c.480C>T
MANE Select: NM_000506
dbSNP: rs3136452
Type: single nucleotide variant
Location: chr11:46723439 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 160: 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

Also linked: thrombophilia due to thrombin defect

For Congenital factor II deficiency (Orphanet):

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

Similar variants

F2 p.Arg461Trp Pathogenic/Likely pathogenic ★★ same condition
F2 p.Arg500Gln Pathogenic ★★ ⚠ same condition
F2 p.Arg581Cys Pathogenic/Likely pathogenic ★★ same condition
F2 p.Arg596Gln Pathogenic ★★ ⚠ same condition
F2 p.Gln387Ter Pathogenic/Likely pathogenic ★★ same condition
F2 c.559+5G>A Uncertain significance ★★ same condition
F2 p.Ala17Ser Uncertain significance ★★ ⚠ same condition
F2 p.Arg117Gln Uncertain significance ★★ ⚠ 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-pro160 (accessed [today's date]).

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