Is F11 p.Asp569= (c.1707C>T) pathogenic?

F11 p.Asp569= (c.1707C>T) is classified Benign in F11 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 9.54%, afr) — too common for a highly-penetrant pathogenic allele; Associated with congenital factor XI deficiency.

What condition is associated with F11 p.Asp569= (c.1707C>T)?

F11 p.Asp569= (c.1707C>T) is associated with congenital factor XI deficiency (ClinVar).

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.Asp569=

Q: How common is F11 p.Asp569= (c.1707C>T) in the general population?

F11 p.Asp569= (c.1707C>T) is common (popmax 9.54%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1707C>T · rs5975 · VCV348380

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 9.54%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

congenital factor XI deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.373	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.5	GERP -4.7
Overall
CADD	4.827	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.54% African / African-American · 7,138/74,844 alleles

Filtering AF 9.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.28%

Overall 0.69% 11,127/1,612,346 alleles · common exomes 6,520/1,460,378 · genomes 4,607/151,968 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.54%	10
Admixed American	4.5%	22
Remaining individualsnot grpmax-eligible	0.96%	104
Middle Eastern	0.512%	195
East Asian	0.388%	258
South Asian	0.0549%	1,821
European (non-Finnish)	0.0367%	2,723
Finnishnot grpmax-eligible	0.00784%	12,752
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,526

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.Asp569=
Coding: c.1707C>T
MANE Select: NM_000128
dbSNP: rs5975
Type: single nucleotide variant
Location: chr4:186287814 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 569: a β-strand; 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.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-asp569 (accessed [today's date]).

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