Is F11 p.Leu167= (c.499C>T) pathogenic?

F11 p.Leu167= (c.499C>T) is classified Uncertain significance in F11 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.000848%, nfe); Associated with congenital factor XI deficiency.

What condition is associated with F11 p.Leu167= (c.499C>T)?

F11 p.Leu167= (c.499C>T) is associated with congenital factor XI deficiency (ClinVar).

How common is F11 p.Leu167= (c.499C>T) in the general population?

F11 p.Leu167= (c.499C>T) is very rare (popmax 0.000848%, nfe) (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.Leu167=

c.499C>T · rs374761594 · VCV348374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Conditions

congenital factor XI deficiency

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
Pangolin	Δ0.20	loss · gain 0.03 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -1.7	GERP -4.4
Overall
CADD	0.042	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000848% European (non-Finnish) · 10/1,179,052 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.00062% 10/1,612,574 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.Leu167=
Coding: c.499C>T
MANE Select: NM_000128
dbSNP: rs374761594
Type: single nucleotide variant
Location: chr4:186275800 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 167: a β-strand; a disulfide bond; the apple 2 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.1481-1G>T Likely pathogenic ★★ same condition
F11 c.1716+1G>A Pathogenic ★★ same condition
F11 c.325+1G>A Pathogenic ★★ same condition
F11 c.326-1G>A Pathogenic ★★ same condition
F11 c.755+2T>C Pathogenic ★★ same condition
F11 c.865+2T>C Likely pathogenic ★★ same condition
F11 p.Ala109Thr Pathogenic ★★ ⚠ same condition
F11 p.Ala430Thr Pathogenic/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-leu167 (accessed [today's date]).

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