Is F10 p.Arg366Cys (c.1096C>T) pathogenic?

F10 p.Arg366Cys (c.1096C>T) is classified Pathogenic in F10 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1989-10-01). AlphaMissense: likely pathogenic (0.8245); Very rare (popmax 0.00167%, amr); Associated with factor X deficiency.

What condition is associated with F10 p.Arg366Cys (c.1096C>T)?

F10 p.Arg366Cys (c.1096C>T) is associated with factor X deficiency (ClinVar).

How common is F10 p.Arg366Cys (c.1096C>T) in the general population?

F10 p.Arg366Cys (c.1096C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about F10 p.Arg366Cys (c.1096C>T)?

AlphaMissense predicts likely pathogenic (score 0.8245) — an in-silico prediction, not a clinical call.

F10 p.Arg366Cys

c.1096C>T · rs104894392 · VCV12053

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8245 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

factor X deficiency

Computational evidence

Protein change
AlphaMissense	0.8245	likely pathogenic ✓ concordant with ClinVar
REVEL	0.716	pathogenic-leaning
SaProt	LLR -11.54	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 4.2	GERP 0.64, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 10 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	27.2	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 · 1/60,004 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000496% 8/1,612,910 alleles · very rare exomes 8/1,460,656 · genomes 0/152,254 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,494
European (non-Finnish)	0.000508%	196,666

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: F10
Protein: p.Arg366Cys
Coding: c.1096C>T
MANE Select: NM_000504
dbSNP: rs104894392
Type: single nucleotide variant
Location: chr13:113149146 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 366: the peptidase s1 domain; a β-strand; a UniProt-annotated variant site (in fa10d; san antonio)

Full F10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

factor X deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

F10 p.Arg366His Uncertain significance ★ ⚠ same residue
F10 p.Glu54Gly Likely pathogenic ★★ same condition
F10 p.Gly21Arg Pathogenic ★★ ⚠ same condition
F10 p.Arg291Gln Uncertain significance ★★ ⚠ same condition
F10 p.Glu69Lys Likely pathogenic ★ same condition
F10 p.Thr358Met Likely pathogenic ★ ⚠ same condition
F10 p.Arg27His Uncertain significance ★ ⚠ same condition
F10 p.Asp463His Uncertain significance ★ ⚠ 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/f10-p-arg366cys (accessed [today's date]).

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