Is F2 p.His429= (c.1287C>T) pathogenic?

F2 p.His429= (c.1287C>T) is classified Likely benign in F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). Very rare (popmax 0.00669%, eas); Associated with congenital prothrombin deficiency.

What condition is associated with F2 p.His429= (c.1287C>T)?

F2 p.His429= (c.1287C>T) is associated with congenital prothrombin deficiency (ClinVar).

How common is F2 p.His429= (c.1287C>T) in the general population?

F2 p.His429= (c.1287C>T) is very rare (popmax 0.00669%, 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.His429=

c.1287C>T · rs1196175175 · VCV2890557

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, 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 0.003	GERP -0.4, phastCons 0.34
Overall
CADD	7.949	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,832 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000249% 4/1,608,960 alleles · very rare exomes 4/1,456,800 · genomes 0/152,160 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,944
South Asian	0.00112%	89,378

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.His429=
Coding: c.1287C>T
MANE Select: NM_000506
dbSNP: rs1196175175
Type: single nucleotide variant
Location: chr11:46728152 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 429: the peptidase s1 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.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-his429 (accessed [today's date]).

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