Is F8 p.Ser1868= (c.5604A>T) pathogenic?

F8 p.Ser1868= (c.5604A>T) is classified Likely benign in F8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-23). Very rare (popmax 0.00404%, nfe); Associated with hemophilia A.

What condition is associated with F8 p.Ser1868= (c.5604A>T)?

F8 p.Ser1868= (c.5604A>T) is associated with hemophilia A (ClinVar).

How common is F8 p.Ser1868= (c.5604A>T) in the general population?

F8 p.Ser1868= (c.5604A>T) is very rare (popmax 0.00404%, nfe) (gnomAD).

How is Hemophilia A inherited?

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

F8 p.Ser1868=

c.5604A>T · rs782028903 · VCV1330605

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00404%, nfe)

Conditions

hemophilia A

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 -3.7	GERP -3.1
Overall
CADD	1.678	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00404% European (non-Finnish) · 36/891,966 alleles

Filtering AF 0.00295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00262%

Overall 0.00323% 39/1,206,202 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00404%	24,777
Admixed American	0.00219%	45,664
Remaining individualsnot grpmax-eligible	0.00211%	47,489
African / African-American	0.00176%	56,951

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: F8
Protein: p.Ser1868=
Coding: c.5604A>T
MANE Select: NM_000132
dbSNP: rs782028903
Type: single nucleotide variant
Location: chrX:154904507 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 1868: the f5/8 type a 3 domain; the plastocyanin-like 5 domain; a disulfide bond; an α-helix

Full F8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hemophilia A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hemophilia A (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

F8 c.6429+2T>A Pathogenic ★★★ same condition
F8 p.Ala111Thr Likely pathogenic ★★★ same condition
F8 p.Ala2220Pro Pathogenic ★★★ same condition
F8 p.Ala415Asp Likely pathogenic ★★★ same condition
F8 p.Ala415Val Pathogenic ★★★ ⚠ same condition
F8 p.Arg1768His Pathogenic ★★★ ⚠ same condition
F8 p.Arg1800His Pathogenic ★★★ same condition
F8 p.Arg2016Trp Pathogenic ★★★ 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/f8-p-ser1868 (accessed [today's date]).

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