Is F11 p.Trp519Ser (c.1556G>C) pathogenic?

F11 p.Trp519Ser (c.1556G>C) is classified Likely pathogenic in F11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely pathogenic (0.9343); Absent from gnomAD v4.1; Associated with Plasma factor XI deficiency.

What condition is associated with F11 p.Trp519Ser (c.1556G>C)?

F11 p.Trp519Ser (c.1556G>C) is associated with Plasma factor XI deficiency (ClinVar).

How common is F11 p.Trp519Ser (c.1556G>C) in the general population?

F11 p.Trp519Ser (c.1556G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F11 p.Trp519Ser (c.1556G>C)?

AlphaMissense predicts likely pathogenic (score 0.9343) — an in-silico prediction, not a clinical call.

F11 p.Trp519Ser

c.1556G>C · VCV4817493

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9343 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Plasma factor XI deficiency

Computational evidence

Protein change
AlphaMissense	0.9343	likely pathogenic ✓ concordant with ClinVar · top 5% in F11
REVEL	0.938	strongly pathogenic-leaning
SaProt	LLR -14.82	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 9.4	GERP 1.3, phastCons 1
Overall
CADD	29.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: F11
Protein: p.Trp519Ser
Coding: c.1556G>C
MANE Select: NM_000128
Type: single nucleotide variant
Location: chr4:186286490 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 519: a β-strand; 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

Similar variants

F11 p.Trp519Cys Pathogenic/Likely pathogenic ★★ same residue
F11 p.Trp519Ter 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

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-trp519ser (accessed [today's date]).

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