Is F2 p.Thr78= (c.234G>A) pathogenic?

F2 p.Thr78= (c.234G>A) is classified Conflicting classifications of pathogenicity in F2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-03). Ultra-rare (popmax 0.0474%, nfe); Associated with Inborn genetic diseases.

What condition is associated with F2 p.Thr78= (c.234G>A)?

F2 p.Thr78= (c.234G>A) is associated with Inborn genetic diseases, thrombophilia due to thrombin defect, congenital prothrombin deficiency (ClinVar).

How common is F2 p.Thr78= (c.234G>A) in the general population?

F2 p.Thr78= (c.234G>A) is ultra-rare (popmax 0.0474%, nfe) (gnomAD).

F2 p.Thr78=

c.234G>A · rs151121282 · VCV878743

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0474%, nfe)

Conditions

Inborn genetic diseases

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 -15	GERP -3.5
Overall
CADD	0.094	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0474% European (non-Finnish) · 548/1,156,326 alleles

Filtering AF 0.0441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0427%

Overall 0.0373% 584/1,565,814 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0474%	2,110
Middle Eastern	0.0385%	2,596
Remaining individualsnot grpmax-eligible	0.0214%	4,672
African / African-American	0.0135%	7,396
Admixed American	0.00952%	10,508
Finnishnot grpmax-eligible	0.00498%	20,072
South Asian	0.00353%	28,289

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.Thr78=
Coding: c.234G>A
MANE Select: NM_000506
dbSNP: rs151121282
Type: single nucleotide variant
Location: chr11:46719856 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 78: the gla domain; an α-helix

Full F2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: thrombophilia due to thrombin defect congenital prothrombin deficiency

Similar variants

F2 p.Thr78Met 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-thr78 (accessed [today's date]).

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