Is F11 p.Val540fs (c.1617dup) pathogenic?

F11 p.Val540fs (c.1617dup) is classified Likely pathogenic in F11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). Associated with Plasma factor XI deficiency.

What condition is associated with F11 p.Val540fs (c.1617dup)?

F11 p.Val540fs (c.1617dup) is associated with Plasma factor XI deficiency (ClinVar).

F11 p.Val540fs

c.1617dup · VCV4817494

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Plasma 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 14 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1

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

Variant & gene context

Gene: F11
Protein: p.Val540fs
Coding: c.1617dup
MANE Select: NM_000128
Type: Duplication
Location: chr4:186287723 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 540: a disulfide bond; the peptidase s1 domain

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

Disease context

Plasma factor XI deficiency

Similar variants

F11 p.Cys103Ter Pathogenic/Likely pathogenic ★★ same condition
F11 p.Tyr52Ter Likely pathogenic ★★ same condition
F11 p.Tyr521fs Pathogenic ★ same condition
F11 c.1136-1G>C Likely pathogenic ★★ same condition
F11 c.1136-7_1136-4del Pathogenic ★★ same condition
F11 c.1481-1G>T Likely pathogenic ★★ same condition
F11 c.1716+1G>A Pathogenic ★★ same condition
F11 c.325+1G>A 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-val540fs (accessed [today's date]).

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