Is F10 p.Cys404Arg (c.1210T>C) pathogenic?

F10 p.Cys404Arg (c.1210T>C) is classified Likely pathogenic in F10 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-01). AlphaMissense: likely pathogenic (0.9982); Very rare (popmax 0.00329%, sas); Associated with congenital factor X deficiency.

What condition is associated with F10 p.Cys404Arg (c.1210T>C)?

F10 p.Cys404Arg (c.1210T>C) is associated with congenital factor X deficiency (ClinVar).

How common is F10 p.Cys404Arg (c.1210T>C) in the general population?

F10 p.Cys404Arg (c.1210T>C) is very rare (popmax 0.00329%, sas) (gnomAD).

How is Congenital factor X deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about F10 p.Cys404Arg (c.1210T>C)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

F10 p.Cys404Arg

c.1210T>C · rs1595099645 · VCV626923

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital factor X deficiency

Computational evidence

Protein change
AlphaMissense	0.9982	likely pathogenic ✓ concordant with ClinVar · top 1% in F10
REVEL	0.977	strongly pathogenic-leaning
SaProt	LLR -17.72	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 10 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	29.7	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

Grpmax group 0.00329% South Asian · 3/91,084 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000205% 3/1,460,906 alleles · very rare

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.Cys404Arg
Coding: c.1210T>C
MANE Select: NM_000504
dbSNP: rs1595099645
Type: single nucleotide variant
Location: chr13:113149260 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 404: the peptidase s1 domain; a β-strand; a disulfide bond; a UniProt-annotated variant site (in fa10d)

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

Disease context

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

For Congenital factor X deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

F10 p.Glu54Gly Likely pathogenic ★★ same condition
F10 p.Gly363Ser Likely pathogenic ★★ same condition
F10 p.Gly450Arg Likely pathogenic ★★ same condition
F10 p.Arg291Gln Uncertain significance ★★ ⚠ same condition
F10 p.Glu306Lys Uncertain significance ★★ ⚠ same condition
F10 p.Gly106= Uncertain significance ★★ same condition
F10 p.Gly154Arg Uncertain significance ★★ ⚠ same condition
F10 p.Pro472Leu 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-cys404arg (accessed [today's date]).

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