Is F11 p.Glu565Lys (c.1693G>A) pathogenic?

F11 p.Glu565Lys (c.1693G>A) is classified Conflicting classifications of pathogenicity in F11 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-07-30). AlphaMissense: likely benign (0.1348); Ultra-rare (popmax 0.0164%, mid); Associated with Plasma factor XI deficiency.

What condition is associated with F11 p.Glu565Lys (c.1693G>A)?

F11 p.Glu565Lys (c.1693G>A) is associated with Plasma factor XI deficiency, congenital factor XI deficiency (ClinVar).

How common is F11 p.Glu565Lys (c.1693G>A) in the general population?

F11 p.Glu565Lys (c.1693G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about F11 p.Glu565Lys (c.1693G>A)?

AlphaMissense predicts likely benign (score 0.1348) — an in-silico prediction, not a clinical call.

F11 p.Glu565Lys

c.1693G>A · rs281875275 · VCV68186

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1348 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Plasma factor XI deficiency

Computational evidence

Protein change
AlphaMissense	0.1348	likely benign
REVEL	0.652	pathogenic-leaning
SaProt	LLR -8.03	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ1.00 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.3	GERP 2.4, phastCons 1
Overall
CADD	22.9	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000558% 9/1,613,106 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.0032%	31,215
East Asian	0.00223%	44,862
European (non-Finnish)	0.000424%	235,889

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.Glu565Lys
Coding: c.1693G>A
MANE Select: NM_001322131 · reported on NM_000128
dbSNP: rs281875275
Type: single nucleotide variant
Location: chr4:186287800 (GRCh38)
Structure: AlphaFold pLDDT 68.98

Full F11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Plasma factor XI deficiency

Also linked: congenital factor XI deficiency

Similar variants

F11 c.1136-1G>C Likely pathogenic ★★ same condition
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.595+3A>G Pathogenic/Likely pathogenic ★★ same condition
F11 c.755+2T>C Pathogenic ★★ same condition
F11 c.865+2T>C 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-glu565lys (accessed [today's date]).

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