Is F2 p.Thr545= (c.1635T>G) pathogenic?

F2 p.Thr545= (c.1635T>G) is classified Likely benign in F2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-14). Rare (popmax 0.12%, eas); Associated with congenital prothrombin deficiency.

What condition is associated with F2 p.Thr545= (c.1635T>G)?

F2 p.Thr545= (c.1635T>G) is associated with congenital prothrombin deficiency (ClinVar).

How common is F2 p.Thr545= (c.1635T>G) in the general population?

F2 p.Thr545= (c.1635T>G) is rare (popmax 0.12%, 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.Thr545=

c.1635T>G · rs200301868 · VCV2750567

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.12%, 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 -20	GERP -3.8
Overall
CADD	0.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.12% East Asian · 54/44,848 alleles

Filtering AF 0.0947% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0855%

Overall 0.00341% 55/1,613,662 alleles · rare exomes 49/1,461,448 · genomes 6/152,214 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.12%	831
South Asian	0.0011%	91,082

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.Thr545=
Coding: c.1635T>G
MANE Select: NM_000506
dbSNP: rs200301868
Type: single nucleotide variant
Location: chr11:46729542 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 545: the peptidase s1 domain; an α-helix

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.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.Arg124Gln 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-thr545 (accessed [today's date]).

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