Is F11 p.Val444fs (c.1329del) pathogenic?

F11 p.Val444fs (c.1329del) is classified Likely pathogenic in F11 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-02-07). Very rare (popmax 0.00133%, afr); Associated with congenital factor XI deficiency.

What condition is associated with F11 p.Val444fs (c.1329del)?

F11 p.Val444fs (c.1329del) is associated with congenital factor XI deficiency (ClinVar).

How common is F11 p.Val444fs (c.1329del) in the general population?

F11 p.Val444fs (c.1329del) is very rare (popmax 0.00133%, afr) (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.Val444fs

c.1329del · rs1554083727 · VCV550660

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 12 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -0.98, phastCons 0.79

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,006 alleles

Overall 6.84e-05% 1/1,461,824 alleles · very rare

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: F11
Protein: p.Val444fs
Coding: c.1329del
MANE Select: NM_000128
dbSNP: rs1554083727
Type: Deletion
Location: chr4:186285662 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 444: 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 c.1136-7_1136-4del Pathogenic ★★ same condition
F11 p.Gly303fs Pathogenic ★★ same condition
F11 p.Ile215_Asp216del Pathogenic/Likely pathogenic ★★ same condition
F11 p.Ile359fs Pathogenic ★★ same condition
F11 p.Leu442fs Pathogenic ★★ same condition
F11 p.Tyr115fs Likely pathogenic ★★ same condition
F11 c.596-7_600del Likely pathogenic ★ same condition
F11 p.Ala223fs 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-val444fs (accessed [today's date]).

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