Is F2 p.Thr114= (c.342G>A) pathogenic?

F2 p.Thr114= (c.342G>A) is classified Likely benign in F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-19). Ultra-rare (popmax 0.01%, amr); Associated with congenital prothrombin deficiency.

What condition is associated with F2 p.Thr114= (c.342G>A)?

F2 p.Thr114= (c.342G>A) is associated with congenital prothrombin deficiency (ClinVar).

How common is F2 p.Thr114= (c.342G>A) in the general population?

F2 p.Thr114= (c.342G>A) is ultra-rare (popmax 0.01%, amr) (gnomAD).

How is Congenital factor II deficiency inherited?

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

F2 p.Thr114=

c.342G>A · rs764153743 · VCV2892905

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

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	all four deltas below 0.2 · G>T here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.62	GERP -0.32, phastCons 0.075
Overall
CADD	4.932	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,992 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000929% 15/1,613,906 alleles · ultra-rare exomes 9/1,461,796 · genomes 6/152,110 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,999
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000678%	147,504

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.Thr114=
Coding: c.342G>A
MANE Select: NM_000506
dbSNP: rs764153743
Type: single nucleotide variant
Location: chr11:46723205 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 114: the kringle 1 domain; a turn

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-thr114 (accessed [today's date]).

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