Is F11 p.Cys500Trp (c.1500C>G) pathogenic?

F11 p.Cys500Trp (c.1500C>G) is classified Pathogenic/Likely pathogenic in F11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-23). AlphaMissense: likely pathogenic (0.905); Very rare (popmax 0.00223%, eas); Associated with Plasma factor XI deficiency.

What condition is associated with F11 p.Cys500Trp (c.1500C>G)?

F11 p.Cys500Trp (c.1500C>G) is associated with Plasma factor XI deficiency, congenital factor XI deficiency (ClinVar).

How common is F11 p.Cys500Trp (c.1500C>G) in the general population?

F11 p.Cys500Trp (c.1500C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about F11 p.Cys500Trp (c.1500C>G)?

AlphaMissense predicts likely pathogenic (score 0.905) — an in-silico prediction, not a clinical call.

F11 p.Cys500Trp

c.1500C>G · VCV4081656

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.905 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Plasma factor XI deficiency

Computational evidence

Protein change
AlphaMissense	0.905	likely pathogenic ✓ concordant with ClinVar · top 7% in F11
REVEL	0.874	moderately pathogenic-leaning
SaProt	LLR -11.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.006	GERP -2.8, phastCons 0.68
Overall
CADD	23.7	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 0.00223% East Asian · 1/44,862 alleles

Overall 6.84e-05% 1/1,461,622 alleles · very rare

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.Cys500Trp
Coding: c.1500C>G
MANE Select: NM_000128
Type: single nucleotide variant
Location: chr4:186286434 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 500: a disulfide bond; the peptidase s1 domain

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 p.Cys500Arg Likely pathogenic ★ ⚠ same residue
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

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-cys500trp (accessed [today's date]).

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