Is F10 p.Tyr449= (c.1347C>T) pathogenic?

F10 p.Tyr449= (c.1347C>T) is classified Uncertain significance in F10 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.0011%, sas); Associated with congenital factor X deficiency.

What condition is associated with F10 p.Tyr449= (c.1347C>T)?

F10 p.Tyr449= (c.1347C>T) is associated with congenital factor X deficiency (ClinVar).

How common is F10 p.Tyr449= (c.1347C>T) in the general population?

F10 p.Tyr449= (c.1347C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Congenital factor X deficiency inherited?

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

F10 p.Tyr449=

c.1347C>T · rs1432439347 · VCV880649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

congenital factor X deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.8
Overall
CADD	1.009	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,072 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,066 alleles · very rare exomes 3/1,460,828 · genomes 1/152,238 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,072
European (non-Finnish)	0.000254%	393,247

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.Tyr449=
Coding: c.1347C>T
MANE Select: NM_000504
dbSNP: rs1432439347
Type: single nucleotide variant
Location: chr13:113149397 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 449: the peptidase s1 domain

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-tyr449 (accessed [today's date]).

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