Is F10 p.Arg287Trp (c.859A>T) pathogenic?

F10 p.Arg287Trp (c.859A>T) is classified Pathogenic in F10 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2000-02-01). AlphaMissense: ambiguous (0.4297); Absent from gnomAD v4.1; Associated with factor X deficiency.

What condition is associated with F10 p.Arg287Trp (c.859A>T)?

F10 p.Arg287Trp (c.859A>T) is associated with factor X deficiency (ClinVar).

How common is F10 p.Arg287Trp (c.859A>T) in the general population?

F10 p.Arg287Trp (c.859A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F10 p.Arg287Trp (c.859A>T)?

AlphaMissense predicts ambiguous (score 0.4297) — an in-silico prediction, not a clinical call.

F10 p.Arg287Trp

c.859A>T · rs121964948 · VCV12059

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4297 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

factor X deficiency

Computational evidence

Protein change
AlphaMissense	0.4297	ambiguous
REVEL	0.726	pathogenic-leaning
SaProt	LLR -9.81	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.80	donor loss, 4 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 3.1	GERP 0.42, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 10 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	24.7	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

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: F10
Protein: p.Arg287Trp
Coding: c.859A>T
MANE Select: NM_000504
dbSNP: rs121964948
Type: single nucleotide variant
Location: chr13:113147490 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 287: the peptidase s1 domain; a β-strand; a disulfide bond

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.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
F10 p.Cys277Ser 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-arg287trp (accessed [today's date]).

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