Is F11 p.Arg396Cys (c.1186C>T) pathogenic?

F11 p.Arg396Cys (c.1186C>T) is classified Pathogenic/Likely pathogenic in F11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-24). AlphaMissense: likely benign (0.0992); Ultra-rare (popmax 0.0164%, mid); Associated with Plasma factor XI deficiency.

What condition is associated with F11 p.Arg396Cys (c.1186C>T)?

F11 p.Arg396Cys (c.1186C>T) is associated with Plasma factor XI deficiency, congenital factor XI deficiency (ClinVar).

How common is F11 p.Arg396Cys (c.1186C>T) in the general population?

F11 p.Arg396Cys (c.1186C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about F11 p.Arg396Cys (c.1186C>T)?

AlphaMissense predicts likely benign (score 0.0992) — an in-silico prediction, not a clinical call.

F11 p.Arg396Cys

c.1186C>T · rs771896253 · VCV188760

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0992 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Plasma factor XI deficiency

Computational evidence

Protein change
AlphaMissense	0.0992	likely benign ⚠ discordant with ClinVar
REVEL	0.542	indeterminate
SaProt	LLR -10.91	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 0.93	GERP -1.7
Overall
CADD	18.23	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 · 1/6,084 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000867% 14/1,614,078 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Admixed American	0.00833%	12,002
East Asian	0.00446%	22,437
South Asian	0.0022%	45,538
European (non-Finnish)	0.000339%	295,013

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.Arg396Cys
Coding: c.1186C>T
MANE Select: NM_001322131 · reported on NM_000128
dbSNP: rs771896253
Type: single nucleotide variant
Location: chr4:186284142 (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 p.Arg396= 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-arg396cys (accessed [today's date]).

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