Is F11 p.Asp143= (c.429C>T) pathogenic?

F11 p.Asp143= (c.429C>T) is classified Benign/Likely benign in F11 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-05-04). Common (popmax 15%, afr) — too common for a highly-penetrant pathogenic allele; Associated with congenital factor XI deficiency.

What condition is associated with F11 p.Asp143= (c.429C>T)?

F11 p.Asp143= (c.429C>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.Asp143=

Q: How common is F11 p.Asp143= (c.429C>T) in the general population?

F11 p.Asp143= (c.429C>T) is common (popmax 15%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.429C>T · rs5973 · VCV255180

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 15%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.6	GERP -4
Overall
CADD	5.133	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15% African / African-American · 11,262/74,996 alleles

Filtering AF 14.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.7%

Overall 3.4% 54,837/1,614,124 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	15%	7
Middle Eastern	6.22%	16
Remaining individualsnot grpmax-eligible	3.78%	26
Ashkenazi Jewishnot grpmax-eligible	3.46%	29
Amishnot grpmax-eligible	3.07%	33
European (non-Finnish)	3.04%	33
Admixed American	2.95%	34
Finnishnot grpmax-eligible	2.03%	49
South Asian	0.935%	107
East Asian	0.00446%	22,443

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.Asp143=
Coding: c.429C>T
MANE Select: NM_000128
dbSNP: rs5973
Type: single nucleotide variant
Location: chr4:186274219 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 143: 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-asp143 (accessed [today's date]).

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