Is F8 p.Pro1560Ser (c.4678C>T) pathogenic?

F8 p.Pro1560Ser (c.4678C>T) is classified Likely benign in F8 (ClinVar, Expert panel, 1 submitter; last evaluated 2026-02-06). AlphaMissense: likely benign (0.0996); Very rare (popmax 0.00324%, nfe); Associated with hemophilia A.

What condition is associated with F8 p.Pro1560Ser (c.4678C>T)?

F8 p.Pro1560Ser (c.4678C>T) is associated with hemophilia A (ClinVar).

How common is F8 p.Pro1560Ser (c.4678C>T) in the general population?

F8 p.Pro1560Ser (c.4678C>T) is very rare (popmax 0.00324%, nfe) (gnomAD).

How is Hemophilia A inherited?

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

What do computational predictors say about F8 p.Pro1560Ser (c.4678C>T)?

AlphaMissense predicts likely benign (score 0.0996) — an in-silico prediction, not a clinical call.

F8 p.Pro1560Ser

c.4678C>T · VCV4849495

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00324%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hemophilia A

Computational evidence

Protein change
AlphaMissense	0.0996	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -5.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.012	GERP -2.5
Regional constraint	o/e 0.99	unconstrained · MANE · 2,842 bp · p 0.74 · regional, not allelic
Overall
CADD	0.188	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 0.00324% European (non-Finnish) · 29/895,132 alleles

Filtering AF 0.00227% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00197%

Overall 0.00248% 30/1,209,516 alleles · very rare exomes 29/1,098,171 · genomes 1/111,345 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00324%	30,867
Remaining individualsnot grpmax-eligible	0.0021%	47,587

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.Pro1560Ser
Coding: c.4678C>T
MANE Select: NM_000132
Type: single nucleotide variant
Location: chrX:154929112 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 1560: the 'b' region

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 p.Pro1560Arg Likely benign ★ same residue
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

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-pro1560ser (accessed [today's date]).

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