Is F8 p.Pro1560Arg (c.4679C>G) pathogenic?

F8 p.Pro1560Arg (c.4679C>G) is classified Likely benign in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely benign (0.1016); Ultra-rare (popmax 0.0846%, sas); Associated with hemophilia A.

What condition is associated with F8 p.Pro1560Arg (c.4679C>G)?

F8 p.Pro1560Arg (c.4679C>G) is associated with hemophilia A (ClinVar).

How common is F8 p.Pro1560Arg (c.4679C>G) in the general population?

F8 p.Pro1560Arg (c.4679C>G) is ultra-rare (popmax 0.0846%, sas) (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.Pro1560Arg (c.4679C>G)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

F8 p.Pro1560Arg

c.4679C>G · rs782791962 · VCV914833

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0846%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hemophilia A

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.72, phastCons 0.45
Regional constraint	o/e 0.99	unconstrained · MANE · 2,842 bp · p 0.74 · regional, not allelic
Overall
CADD	9.662	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 0.0846% South Asian · 48/56,765 alleles

Filtering AF 0.0654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0587%

Overall 0.0043% 52/1,209,713 alleles · ultra-rare exomes 50/1,098,179 · genomes 2/111,534 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0846%	1,183
Remaining individualsnot grpmax-eligible	0.0084%	11,900

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.Pro1560Arg
Coding: c.4679C>G
MANE Select: NM_000132
dbSNP: rs782791962
Type: single nucleotide variant
Location: chrX:154929111 (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.Pro1560Ser 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-pro1560arg (accessed [today's date]).

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