Is F11 p.Thr428fs (c.1275_1281dup) pathogenic?

F11 p.Thr428fs (c.12751281dup) is classified Pathogenic in F11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-06-30). No gnomAD frequency available for this variant; Associated with congenital factor XI deficiency.

What condition is associated with F11 p.Thr428fs (c.1275_1281dup)?

F11 p.Thr428fs (c.1275_1281dup) is associated with congenital factor XI deficiency (ClinVar).

How common is F11 p.Thr428fs (c.1275_1281dup) in the general population?

F11 p.Thr428fs (c.1275_1281dup) is no gnomAD frequency available for this variant (gnomAD).

How is Congenital factor XI deficiency inherited?

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

F11 p.Thr428fs

c.1275_1281dup · rs1580098946 · VCV659228

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

congenital factor XI deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.5	GERP 1.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: F11
Protein: p.Thr428fs
Coding: c.1275_1281dup
MANE Select: NM_000128
dbSNP: rs1580098946
Type: Duplication
Location: chr4:186284230 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 428: a β-strand; a disulfide bond; the peptidase s1 domain

Full F11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital factor XI deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital factor XI deficiency (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

F11 p.Thr428Ile Uncertain significance ⚠ same residue
F11 p.Tyr52Ter Likely pathogenic ★★ same condition
F11 p.Ile164fs Likely pathogenic ★ same condition
F11 p.Thr240fs Pathogenic ★ same condition
F11 p.Tyr521fs Pathogenic ★ same condition
F11 p.Asn491fs Likely pathogenic same condition
F11 p.Thr331fs Likely pathogenic same condition
F11 p.Thr541fs Likely pathogenic 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/f11-p-thr428fs (accessed [today's date]).

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