Is F2 p.Thr64= (c.192G>C) pathogenic?

F2 p.Thr64= (c.192G>C) is classified Likely benign in F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). Very rare (popmax 0.00228%, eas); Associated with congenital prothrombin deficiency.

What condition is associated with F2 p.Thr64= (c.192G>C)?

F2 p.Thr64= (c.192G>C) is associated with congenital prothrombin deficiency (ClinVar).

How common is F2 p.Thr64= (c.192G>C) in the general population?

F2 p.Thr64= (c.192G>C) is very rare (popmax 0.00228%, eas) (gnomAD).

How is Congenital factor II deficiency inherited?

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

F2 p.Thr64=

c.192G>C · rs147253030 · VCV2907841

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00228%, eas)

Conditions

congenital prothrombin 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 0.44	GERP -1.4, phastCons 0.016
Overall
CADD	1.952	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00228% East Asian · 1/43,938 alleles

Overall 0.000126% 2/1,591,114 alleles · very rare exomes 2/1,438,798 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00228%	43,938
Admixed American	0.00178%	56,204

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.Thr64=
Coding: c.192G>C
MANE Select: NM_000506
dbSNP: rs147253030
Type: single nucleotide variant
Location: chr11:46719814 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 64: the gla 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.Thr64Met Uncertain significance ★★ ⚠ same residue
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

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-thr64 (accessed [today's date]).

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