Is F11 p.Glu620Gln (c.1858G>C) pathogenic?

F11 p.Glu620Gln (c.1858G>C) is classified Conflicting classifications of pathogenicity in F11 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.1027); Ultra-rare (popmax 0.099%, mid); Associated with congenital factor XI deficiency.

What condition is associated with F11 p.Glu620Gln (c.1858G>C)?

F11 p.Glu620Gln (c.1858G>C) is associated with congenital factor XI deficiency (ClinVar).

How common is F11 p.Glu620Gln (c.1858G>C) in the general population?

F11 p.Glu620Gln (c.1858G>C) is ultra-rare (popmax 0.099%, mid) (gnomAD).

How is Congenital factor XI deficiency inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about F11 p.Glu620Gln (c.1858G>C)?

AlphaMissense predicts likely benign (score 0.1027) — an in-silico prediction, not a clinical call.

F11 p.Glu620Gln

c.1858G>C · rs148054334 · VCV1050220

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1027 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.099%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor XI deficiency

Computational evidence

Protein change
AlphaMissense	0.1027	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 0.38, phastCons 1
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.099% Middle Eastern · 6/6,062 alleles

Filtering AF 0.043% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0294%

Overall 0.0144% 233/1,614,124 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.099%	1,010
Admixed American	0.045%	2,223
Remaining individualsnot grpmax-eligible	0.0384%	2,604
European (non-Finnish)	0.0146%	6,860
African / African-American	0.00533%	18,763

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.Glu620Gln
Coding: c.1858G>C
MANE Select: NM_001322131 · reported on NM_000128
dbSNP: rs148054334
Type: single nucleotide variant
Location: chr4:186288594 (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.Pro620Leu 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-glu620gln (accessed [today's date]).

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