Is F11 p.Thr267= (c.801A>G) pathogenic?

F11 p.Thr267= (c.801A>G) is classified Benign/Likely benign in F11 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-05-04). Common (popmax 21.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with congenital factor XI deficiency.

What condition is associated with F11 p.Thr267= (c.801A>G)?

F11 p.Thr267= (c.801A>G) 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.Thr267=

Q: How common is F11 p.Thr267= (c.801A>G) in the general population?

F11 p.Thr267= (c.801A>G) is common (popmax 21.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.801A>G · rs5974 · VCV255181

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 21.4%, 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	0.013	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -4.7
Overall
CADD	0.622	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 21.4% African / African-American · 16,042/74,954 alleles

Filtering AF 21.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 21%

Overall 14.5% 234,202/1,613,478 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	22%	5
African / African-Americangrpmax	21.4%	5
South Asian	20.4%	5
Middle Eastern	19.4%	5
Finnishnot grpmax-eligible	16.2%	6
Ashkenazi Jewishnot grpmax-eligible	15.8%	6
Remaining individualsnot grpmax-eligible	14.9%	7
European (non-Finnish)	14%	7
Admixed American	11%	9
East Asian	4.71%	21

Amish 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.Thr267=
Coding: c.801A>G
MANE Select: NM_001322131 · reported on NM_000128
dbSNP: rs5974
Type: single nucleotide variant
Location: chr4:186280057 (GRCh38)
Structure: AlphaFold pLDDT 68.98

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

ZNF160 p.Thr267Ile Uncertain significance ★ ⚠ same residue
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

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-thr267 (accessed [today's date]).

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