Is F10 p.Phe116= (c.348C>T) pathogenic?

F10 p.Phe116= (c.348C>T) is classified Conflicting classifications of pathogenicity in F10 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-08-24). Ultra-rare (popmax 0.0164%, mid); Associated with congenital factor X deficiency.

What condition is associated with F10 p.Phe116= (c.348C>T)?

F10 p.Phe116= (c.348C>T) is associated with congenital factor X deficiency (ClinVar).

How common is F10 p.Phe116= (c.348C>T) in the general population?

F10 p.Phe116= (c.348C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Congenital factor X deficiency inherited?

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

F10 p.Phe116=

c.348C>T · rs747030511 · VCV311272

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

congenital factor X deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -14	GERP -3.5
Overall
CADD	1.519	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00347% 56/1,613,698 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Admixed American	0.01%	9,995
African / African-American	0.00668%	14,972
Remaining individualsnot grpmax-eligible	0.0064%	15,617
European (non-Finnish)	0.00322%	31,049
South Asian	0.0022%	45,531

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.Phe116=
Coding: c.348C>T
MANE Select: NM_000504
dbSNP: rs747030511
Type: single nucleotide variant
Location: chr13:113139448 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 116: a β-strand; a disulfide bond; the egf-like 1; calcium-binding 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-phe116 (accessed [today's date]).

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