Is F11 p.Arg91Trp (c.271A>T) pathogenic?

F11 p.Arg91Trp (c.271A>T) is classified Uncertain significance in F11 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.1161); Very rare (popmax 0.00167%, amr); Associated with Plasma factor XI deficiency.

What condition is associated with F11 p.Arg91Trp (c.271A>T)?

F11 p.Arg91Trp (c.271A>T) is associated with Plasma factor XI deficiency (ClinVar).

How common is F11 p.Arg91Trp (c.271A>T) in the general population?

F11 p.Arg91Trp (c.271A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about F11 p.Arg91Trp (c.271A>T)?

AlphaMissense predicts likely benign (score 0.1161) — an in-silico prediction, not a clinical call.

F11 p.Arg91Trp

c.271A>T · VCV4067788

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1161 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Plasma factor XI deficiency

Computational evidence

Protein change
AlphaMissense	0.1161	likely benign
REVEL	0.421	indeterminate
SaProt	LLR -10.43	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP 1.2
Overall
CADD	19.66	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 0.00167% Admixed American · 1/60,010 alleles

Overall 0.000124% 2/1,614,000 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Arg91Trp
Coding: c.271A>T
MANE Select: NM_000128
Type: single nucleotide variant
Location: chr4:186273123 (GRCh38)
Gene constraint: LOEUF 1.145 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 117 PDB
Residue 91: a disulfide bond; the apple 1 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.Arg91Met Likely benign ★ 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-arg91trp (accessed [today's date]).

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