Is F11 p.Glu613= (c.1839G>A) pathogenic?

F11 p.Glu613= (c.1839G>A) is classified Benign/Likely benign in F11 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-06-26). Common (popmax 11.3%, mid) — too common for a highly-penetrant pathogenic allele; Associated with congenital factor XI deficiency.

What condition is associated with F11 p.Glu613= (c.1839G>A)?

F11 p.Glu613= (c.1839G>A) 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.Glu613=

Q: How common is F11 p.Glu613= (c.1839G>A) in the general population?

F11 p.Glu613= (c.1839G>A) is common (popmax 11.3%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1839G>A · rs5976 · VCV255179

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 11.3%, mid) — 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	0.041	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 0.53, phastCons 1
Overall
CADD	14.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.3% Middle Eastern · 687/6,060 alleles

Filtering AF 10.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.4%

Overall 4.88% 78,816/1,614,124 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	11.3%	9
Ashkenazi Jewishnot grpmax-eligible	8.2%	12
Amishnot grpmax-eligible	8.11%	12
South Asian	8.11%	12
East Asian	7.97%	13
Admixed American	6.23%	16
Remaining individualsnot grpmax-eligible	5.09%	20
European (non-Finnish)	4.42%	23
African / African-American	4.16%	24
Finnishnot grpmax-eligible	3.83%	26

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.Glu613=
Coding: c.1839G>A
MANE Select: NM_000128
dbSNP: rs5976
Type: single nucleotide variant
Location: chr4:186288575 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 613: an α-helix; 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 p.Glu613Lys Conflicting classifications of pathogenicity ★ ⚠ 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-glu613 (accessed [today's date]).

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