Is F11 p.Ile359fs (c.1075del) pathogenic?

F11 p.Ile359fs (c.1075del) is classified Pathogenic in F11 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-09-09). Very rare (popmax 0.00167%, amr); Associated with Plasma factor XI deficiency.

What condition is associated with F11 p.Ile359fs (c.1075del)?

F11 p.Ile359fs (c.1075del) is associated with Plasma factor XI deficiency, congenital factor XI deficiency (ClinVar).

How common is F11 p.Ile359fs (c.1075del) in the general population?

F11 p.Ile359fs (c.1075del) is very rare (popmax 0.00167%, amr) (gnomAD).

F11 p.Ile359fs

c.1075del · rs786204429 · VCV188727

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.08	GERP -4.4, phastCons 0.76

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,020 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000821% 12/1,461,886 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,837
Admixed Americangrpmax	0.00167%	60,020
European (non-Finnish)	0.000678%	147,504

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile359fs
Coding: c.1075del
MANE Select: NM_001322131 · reported on NM_000128
dbSNP: rs786204429
Type: Deletion
Location: chr4:186280517 (GRCh38)
Structure: AlphaFold pLDDT 68.98

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

Disease context

Plasma factor XI deficiency

Also linked: congenital factor XI deficiency

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.Ile481fs Pathogenic ★★ same condition
F11 p.Leu442fs Pathogenic ★★ same condition
F11 p.Leu483fs Pathogenic/Likely pathogenic ★★ same condition
F11 p.Tyr115fs Likely pathogenic ★★ same condition
F11 c.596-7_600del 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-ile359fs (accessed [today's date]).

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